中心体蛋白Cep70调节微管组织及微管相关细胞活动的分子机制
|
摘要
中心体由一对互相垂直排列的中心粒及围绕在中心粒周围的无定形基质组成，是动物细胞主要的微管组织中心。中心体通过核化、组织微管骨架，调节许多细胞活动包括细胞形态的维持、细胞极性的建立、有丝分裂和细胞迁移等。
Cep70是一个分子量为70kDa，含597个氨基酸的蛋白质，含有两个卷曲螺旋结构域。Cep70最初在人类中心体蛋白质组学的研究中发现，近几年Cep70在不同物种中的生物学功能逐渐被了解。斑马鱼的Cep70调节纤毛发生，从而影响胚胎发育。而且，Cep70家族的成员——衣藻前中心粒蛋白CRC70在中心粒前体的组装中发挥重要作用。但是，哺乳动物细胞中Cep70的定位和功能目前仍不清楚。在本研究中，我们通过免疫荧光实验确定Cep70是一个中心体蛋白。在细胞周期的各个时期，Cep70均定位在中心体上，它通过两个卷曲螺旋结构域与-微管蛋白相互作用。Cep70调节细胞内原有的和新生微管的组织，而且在体外实验中，Cep70促进微管组装。在有丝分裂期，Cep70表达降低使双极纺锤体的组织和定向异常。
中心体蛋白不仅通过介导纺锤体的形成来调节有丝分裂，在其他细胞活动如细胞迁移中也发挥重要作用。本研究发现Cep70通过调节内皮细胞的迁移来影响血管新生。在小鼠体内血管新生实验中，Cep70小干扰RNA显著抑制血管新生。在体外实验中，Cep70表达下调阻碍了内皮细胞在基质胶上的成管能力和在胶原中的出芽生长。在对Cep70调节血管新生的机制研究中，发现Cep70通过介导内皮细胞的极化和迁移来调节血管新生。而且，Cep70表达下调显著降低了迁移细胞前端片状伪足区域膜皱褶的动态性。进一步研究发现，Rho GTP酶家族的Cdc42和Rac1的活化在Cep70调节血管新生中发挥作用。这些结果表明Cep70介导内皮细胞的极化和迁移，从而在血管新生中发挥作用。
概括来说，本研究首次证实Cep70是一个中心体蛋白，通过结合-微管蛋白定位在中心体上。而且，Cep70能调节微管的组织和有丝分裂纺锤体的定向。另外，本研究发现Cep70通过介导血管内皮细胞的极化和迁移而影响血管新生。
The centrosome, composed of a pair of barrel-shaped centrioles surrounded byelectron-dense pericentriolar material, is the major microtubule-organizing center inanimal cells. In addition to its role in the nucleation and organization of microtubules,the centrosome is also critical for the orchestration of cell cycle progression. Toensure bipolar organization and geometric precision of the mitotic spindle, thecentrosome serves as a cellular hub where several key regulators convene to mediatevital interactions that control spindle assembly. The centrosome may also serve toregulate other fundamental cellular functions, such as cell polarity and motility.
Cep70, a candidate centrosomal protein of70kDa, was originally discovered ina proteomic study of the human centrosome. Recently, the biological function ofCep70in different species is beginning to be unraveled. The zebrafish homolog ofCep70has been shown to contribute to the assembly of cilia by determination of thelength of the axoneme. In addition, the Chlamydomonas procentriole protein CRC70,a member of the conserved Cep70family, acts as a scaffold for the assembly of thecentriole precursor. However, the localization and functions of Cep70in mammaliancells remain unknown.
In this study, we report the molecular characterization and functional analysis ofa novel centrosomal protein, Cep70, in mammalian cells. Our data show that Cep70localizes to the centrosome throughout the cell cycle and binds to the key centrosomalcomponent,-tubulin, through the peptide fragments that contain the coiled-coildomains. Our data further reveal that the centrosomal localization pattern of Cep70isdependent on its interaction with-tubulin. Strikingly, Cep70plays a significant rolein the organization of both preexisting and nascent microtubules in interphase cells.Besides, Cep70promotes microtubule assembly in vitro by increasing microtubuleelongation. In addition, Cep70is necessary for the organization and orientation of thebipolar spindle during mitosis. These results thus report for the first time theidentification of Cep70as an important centrosomal protein that interacts with -tubulin and underscore its critical role in the regulation of mitotic spindle assembly.
Centrosomal proteins are important for the organization of microtubules inanimal cells and regulate diverse microtubule-mediated cellular activities such as cellmigration, a critical step in angiogenesis. However, the participation of these proteinsin angiogenesis, which involves vascular endothelial cell migration from preexistingblood vessels, remains elusive. Here, we demonstrate that Cep70is necessary forangiogenic response in mice. This protein is also required for tube formation andcapillary sprouting in vitro from vascular endothelial cells. Wound healing andtranswell assays reveal that Cep70plays a significant role in endothelial cellmigration. Depletion of Cep70results in severe defects in membrane ruffle formationand centrosome reorientation, indicating a requirement for this protein in cellpolarization. In addition, Cep70is critically involved in microtubule rearrangement inresponse to the migratory stimulus. Our data further demonstrate that Cep70isimportant for Cdc42and Rac1activation to promote angiogenesis. These findingsthus establish Cep70as a critical regulator of the angiogenic process and emphasizethe significance of microtubules for vascular endothelial cell migration andangiogenesis.
In conclusion, we describe the characterization of Cep70as a centrosomalprotein and demonstrate its localization to the centrosome throughout the cell cyclevia interaction with-tubulin. We also present evidence that Cep70is a criticalregulator for the organization of radial microtubule arrays and the spindle apparatus.In addition, Cep70is implicated in angiogenesis by regulating vascular endothelialpolarization and migration.
Cep70是一个分子量为70kDa，含597个氨基酸的蛋白质，含有两个卷曲螺旋结构域。Cep70最初在人类中心体蛋白质组学的研究中发现，近几年Cep70在不同物种中的生物学功能逐渐被了解。斑马鱼的Cep70调节纤毛发生，从而影响胚胎发育。而且，Cep70家族的成员——衣藻前中心粒蛋白CRC70在中心粒前体的组装中发挥重要作用。但是，哺乳动物细胞中Cep70的定位和功能目前仍不清楚。在本研究中，我们通过免疫荧光实验确定Cep70是一个中心体蛋白。在细胞周期的各个时期，Cep70均定位在中心体上，它通过两个卷曲螺旋结构域与-微管蛋白相互作用。Cep70调节细胞内原有的和新生微管的组织，而且在体外实验中，Cep70促进微管组装。在有丝分裂期，Cep70表达降低使双极纺锤体的组织和定向异常。
中心体蛋白不仅通过介导纺锤体的形成来调节有丝分裂，在其他细胞活动如细胞迁移中也发挥重要作用。本研究发现Cep70通过调节内皮细胞的迁移来影响血管新生。在小鼠体内血管新生实验中，Cep70小干扰RNA显著抑制血管新生。在体外实验中，Cep70表达下调阻碍了内皮细胞在基质胶上的成管能力和在胶原中的出芽生长。在对Cep70调节血管新生的机制研究中，发现Cep70通过介导内皮细胞的极化和迁移来调节血管新生。而且，Cep70表达下调显著降低了迁移细胞前端片状伪足区域膜皱褶的动态性。进一步研究发现，Rho GTP酶家族的Cdc42和Rac1的活化在Cep70调节血管新生中发挥作用。这些结果表明Cep70介导内皮细胞的极化和迁移，从而在血管新生中发挥作用。
概括来说，本研究首次证实Cep70是一个中心体蛋白，通过结合-微管蛋白定位在中心体上。而且，Cep70能调节微管的组织和有丝分裂纺锤体的定向。另外，本研究发现Cep70通过介导血管内皮细胞的极化和迁移而影响血管新生。
The centrosome, composed of a pair of barrel-shaped centrioles surrounded byelectron-dense pericentriolar material, is the major microtubule-organizing center inanimal cells. In addition to its role in the nucleation and organization of microtubules,the centrosome is also critical for the orchestration of cell cycle progression. Toensure bipolar organization and geometric precision of the mitotic spindle, thecentrosome serves as a cellular hub where several key regulators convene to mediatevital interactions that control spindle assembly. The centrosome may also serve toregulate other fundamental cellular functions, such as cell polarity and motility.
Cep70, a candidate centrosomal protein of70kDa, was originally discovered ina proteomic study of the human centrosome. Recently, the biological function ofCep70in different species is beginning to be unraveled. The zebrafish homolog ofCep70has been shown to contribute to the assembly of cilia by determination of thelength of the axoneme. In addition, the Chlamydomonas procentriole protein CRC70,a member of the conserved Cep70family, acts as a scaffold for the assembly of thecentriole precursor. However, the localization and functions of Cep70in mammaliancells remain unknown.
In this study, we report the molecular characterization and functional analysis ofa novel centrosomal protein, Cep70, in mammalian cells. Our data show that Cep70localizes to the centrosome throughout the cell cycle and binds to the key centrosomalcomponent,-tubulin, through the peptide fragments that contain the coiled-coildomains. Our data further reveal that the centrosomal localization pattern of Cep70isdependent on its interaction with-tubulin. Strikingly, Cep70plays a significant rolein the organization of both preexisting and nascent microtubules in interphase cells.Besides, Cep70promotes microtubule assembly in vitro by increasing microtubuleelongation. In addition, Cep70is necessary for the organization and orientation of thebipolar spindle during mitosis. These results thus report for the first time theidentification of Cep70as an important centrosomal protein that interacts with -tubulin and underscore its critical role in the regulation of mitotic spindle assembly.
Centrosomal proteins are important for the organization of microtubules inanimal cells and regulate diverse microtubule-mediated cellular activities such as cellmigration, a critical step in angiogenesis. However, the participation of these proteinsin angiogenesis, which involves vascular endothelial cell migration from preexistingblood vessels, remains elusive. Here, we demonstrate that Cep70is necessary forangiogenic response in mice. This protein is also required for tube formation andcapillary sprouting in vitro from vascular endothelial cells. Wound healing andtranswell assays reveal that Cep70plays a significant role in endothelial cellmigration. Depletion of Cep70results in severe defects in membrane ruffle formationand centrosome reorientation, indicating a requirement for this protein in cellpolarization. In addition, Cep70is critically involved in microtubule rearrangement inresponse to the migratory stimulus. Our data further demonstrate that Cep70isimportant for Cdc42and Rac1activation to promote angiogenesis. These findingsthus establish Cep70as a critical regulator of the angiogenic process and emphasizethe significance of microtubules for vascular endothelial cell migration andangiogenesis.
In conclusion, we describe the characterization of Cep70as a centrosomalprotein and demonstrate its localization to the centrosome throughout the cell cyclevia interaction with-tubulin. We also present evidence that Cep70is a criticalregulator for the organization of radial microtubule arrays and the spindle apparatus.In addition, Cep70is implicated in angiogenesis by regulating vascular endothelialpolarization and migration.
引文
[1] Bettencourt-Dias M, Glover D M. SnapShot: centriole biogenesis. Cell,2009,136(1):188-188e181
[2] Dictenberg J B, Zimmerman W, Sparks C A, et al. Pericentrin and gamma-tubulin form aprotein complex and are organized into a novel lattice at the centrosome. J Cell Biol,1998,141(1):163-174
[3] Dammermann A, Merdes A. Assembly of centrosomal proteins and microtubuleorganization depends on PCM-1. J Cell Biol,2002,159(2):255-266
[4] Moritz M, Braunfeld M B, Sedat J W, et al. Microtubule nucleation bygamma-tubulin-containing rings in the centrosome. Nature,1995,378(6557):638-640
[5] Delgehyr N, Sillibourne J, Bornens M. Microtubule nucleation and anchoring at thecentrosome are independent processes linked by ninein function. J Cell Sci,2005,118(Pt8):1565-1575
[6] Louie R K, Bahmanyar S, Siemers K A, et al. Adenomatous polyposis coli and EB1localizein close proximity of the mother centriole and EB1is a functional component ofcentrosomes. J Cell Sci,2004,117(Pt7):1117-1128
[7] Yan X, Habedanck R, Nigg E A. A complex of two centrosomal proteins, CAP350and FOP,cooperates with EB1in microtubule anchoring. Mol Biol Cell,2006,17(2):634-644
[8] Guo J, Yang Z, Song W, et al. Nudel contributes to microtubule anchoring at the mothercentriole and is involved in both dynein-dependent and-independent centrosomal proteinassembly. Mol Biol Cell,2006,17(2):680-689
[9] Taylor S, Peters J M. Polo and Aurora kinases: lessons derived from chemical biology. CurrOpin Cell Biol,2008,20(1):77-84
[10] Bettencourt-Dias M, Glover D M. Centrosome biogenesis and function: centrosomicsbrings new understanding. Nat Rev Mol Cell Biol,2007,8(6):451-463
[11] Tokuyama Y, Horn H F, Kawamura K, et al. Specific phosphorylation of nucleophosmin onThr(199) by cyclin-dependent kinase2-cyclin E and its role in centrosome duplication. JBiol Chem,2001,276(24):21529-21537
[12] Okuda M. The role of nucleophosmin in centrosome duplication. Oncogene,2002,21(40):6170-6174
[13] Chen Z, Indjeian V B, McManus M, et al. CP110, a cell cycle-dependent CDK substrate,regulates centrosome duplication in human cells. Dev Cell,2002,3(3):339-350
[14] Geng Y, Lee Y M, Welcker M, et al. Kinase-independent function of cyclin E. Mol Cell,2007,25(1):127-139
[15] Ferguson R L, Maller J L. Cyclin E-dependent localization of MCM5regulates centrosomeduplication. J Cell Sci,2008,121(Pt19):3224-3232
[16] Hemerly A S, Prasanth S G, Siddiqui K, et al. Orc1controls centriole and centrosome copynumber in human cells. Science,2009,323(5915):789-793
[17] Habedanck R, Stierhof Y D, Wilkinson C J, et al. The Polo kinase Plk4functions incentriole duplication. Nat Cell Biol,2005,7(11):1140-1146
[18] Loncarek J, Hergert P, Magidson V, et al. Control of daughter centriole formation by thepericentriolar material. Nat Cell Biol,2008,10(3):322-328
[19] Vladar E K, Stearns T. Molecular characterization of centriole assembly in ciliatedepithelial cells. J Cell Biol,2007,178(1):31-42
[20] Khodjakov A, Rieder C L, Sluder G, et al. De novo formation of centrosomes in vertebratecells arrested during S phase. J Cell Biol,2002,158(7):1171-1181
[21] Haren L, Remy M H, Bazin I, et al. NEDD1-dependent recruitment of the gamma-tubulinring complex to the centrosome is necessary for centriole duplication and spindle assembly.J Cell Biol,2006,172(4):505-515
[22] Zhu F, Lawo S, Bird A, et al. The mammalian SPD-2ortholog Cep192regulatescentrosome biogenesis. Curr Biol,2008,18(2):136-141
[23] O'Toole E T, Giddings T H, McIntosh J R, et al. Three-dimensional organization of basalbodies from wild-type and delta-tubulin deletion strains of Chlamydomonas reinhardtii.Mol Biol Cell,2003,14(7):2999-3012
[24] Pelletier L, O'Toole E, Schwager A, et al. Centriole assembly in Caenorhabditis elegans.Nature,2006,444(7119):619-623
[25] Dutcher S K, Morrissette N S, Preble A M, et al. Epsilon-tubulin is an essential componentof the centriole. Mol Biol Cell,2002,13(11):3859-3869
[26] Strnad P, Leidel S, Vinogradova T, et al. Regulated HsSAS-6levels ensure formation of asingle procentriole per centriole during the centrosome duplication cycle. Dev Cell,2007,13(2):203-213
[27] Zyss D, Gergely F. Centrosome function in cancer: guilty or innocent? Trends Cell Biol,2009,19(7):334-346
[28] Doxsey S, Zimmerman W, Mikule K. Centrosome control of the cell cycle. Trends Cell Biol,2005,15(6):303-311
[29] Neben K, Tews B, Wrobel G, et al. Gene expression patterns in acute myeloid leukemiacorrelate with centrosome aberrations and numerical chromosome changes. Oncogene,2004,23(13):2379-2384
[30] Matsumoto Y, Maller J L. A centrosomal localization signal in cyclin E required forCdk2-independent S phase entry. Science,2004,306(5697):885-888
[31] Luders J, Stearns T. Microtubule-organizing centres: a re-evaluation. Nat Rev Mol Cell Biol,2007,8(2):161-167
[32] O'Connell C B, Khodjakov A L. Cooperative mechanisms of mitotic spindle formation. JCell Sci,2007,120(Pt10):1717-1722
[33] Rebollo E, Sampaio P, Januschke J, et al. Functionally unequal centrosomes drive spindleorientation in asymmetrically dividing Drosophila neural stem cells. Dev Cell,2007,12(3):467-474
[34] Rusan N M, Peifer M. A role for a novel centrosome cycle in asymmetric cell division. JCell Biol,2007,177(1):13-20
[35] Toyoshima F, Nishida E. Integrin-mediated adhesion orients the spindle parallel to thesubstratum in an EB1-and myosin X-dependent manner. EMBO J,2007,26(6):1487-1498
[36] Yamashita Y M, Mahowald A P, Perlin J R, et al. Asymmetric inheritance of mother versusdaughter centrosome in stem cell division. Science,2007,315(5811):518-521
[37] Rieder C L, Faruki S, Khodjakov A. The centrosome in vertebrates: more than amicrotubule-organizing center. Trends Cell Biol,2001,11(10):413-419
[38] Desai A, Mitchison T J. Microtubule polymerization dynamics. Annu Rev Cell Dev Biol,1997,13:83-117
[39] Nogales E, Wolf S G, Downing K H. Structure of the alpha beta tubulin dimer by electroncrystallography. Nature,1998,391(6663):199-203
[40] Lowe J, Li H, Downing K H, et al. Refined structure of alpha beta-tubulin at3.5Aresolution. J Mol Biol,2001,313(5):1045-1057
[41] Tuszynski J A, Carpenter E J, Huzil J T, et al. The evolution of the structure of tubulin andits potential consequences for the role and function of microtubules in cells and embryos.Int J Dev Biol,2006,50(2-3):341-358
[42] Conde C, Caceres A. Microtubule assembly, organization and dynamics in axons anddendrites. Nat Rev Neurosci,2009,10(5):319-332
[43] Westermann S, Weber K. Post-translational modifications regulate microtubule function.Nat Rev Mol Cell Biol,2003,4(12):938-947
[44] Mostowy S, Cossart P. Septins: the fourth component of the cytoskeleton. Nat Rev Mol CellBiol,2012,13(3):183-194
[45] Zheng Y, Wong M L, Alberts B, et al. Nucleation of microtubule assembly by agamma-tubulin-containing ring complex. Nature,1995,378(6557):578-583
[46] Gunawardane R N, Martin O C, Cao K, et al. Characterization and reconstitution ofDrosophila gamma-tubulin ring complex subunits. J Cell Biol,2000,151(7):1513-1524
[47] Murphy S M, Preble A M, Patel U K, et al. GCP5and GCP6: two new members of thehuman gamma-tubulin complex. Mol Biol Cell,2001,12(11):3340-3352
[48] Murphy S M, Urbani L, Stearns T. The mammalian gamma-tubulin complex containshomologues of the yeast spindle pole body components spc97p and spc98p. J Cell Biol,1998,141(3):663-674
[49] Teixido-Travesa N, Villen J, Lacasa C, et al. The gammaTuRC revisited: a comparativeanalysis of interphase and mitotic human gammaTuRC redefines the set of core componentsand identifies the novel subunit GCP8. Mol Biol Cell,2010,21(22):3963-3972
[50] Hutchins J R, Toyoda Y, Hegemann B, et al. Systematic analysis of human proteincomplexes identifies chromosome segregation proteins. Science,2010,328(5978):593-599
[51] Oegema K, Wiese C, Martin O C, et al. Characterization of two related Drosophilagamma-tubulin complexes that differ in their ability to nucleate microtubules. J Cell Biol,1999,144(4):721-733
[52] Kollman J M, Merdes A, Mourey L, et al. Microtubule nucleation by gamma-tubulincomplexes. Nat Rev Mol Cell Biol,2011,12(11):709-721
[53] Nigg E A, Raff J W. Centrioles, centrosomes, and cilia in health and disease. Cell,2009,139(4):663-678
[54] Lingle W L, Lutz W H, Ingle J N, et al. Centrosome hypertrophy in human breast tumors:implications for genomic stability and cell polarity. Proc Natl Acad Sci U S A,1998,95(6):2950-2955
[55] Pihan G A, Purohit A, Wallace J, et al. Centrosome defects and genetic instability inmalignant tumors. Cancer Res,1998,58(17):3974-3985
[56] Weber R G, Bridger J M, Benner A, et al. Centrosome amplification as a possiblemechanism for numerical chromosome aberrations in cerebral primitive neuroectodermaltumors with TP53mutations. Cytogenet Cell Genet,1998,83(3-4):266-269
[57] Pihan G A, Purohit A, Wallace J, et al. Centrosome defects can account for cellular andgenetic changes that characterize prostate cancer progression. Cancer Res,2001,61(5):2212-2219
[58] Lingle W L, Salisbury J L. Altered centrosome structure is associated with abnormalmitoses in human breast tumors. Am J Pathol,1999,155(6):1941-1951
[59] Sato N, Mizumoto K, Nakamura M, et al. Centrosome abnormalities in pancreatic ductalcarcinoma. Clin Cancer Res,1999,5(5):963-970
[60] Sato N, Mizumoto K, Nakamura M, et al. Correlation between centrosome abnormalitiesand chromosomal instability in human pancreatic cancer cells. Cancer Genet Cytogenet,2001,126(1):13-19
[61] Kuo K K, Sato N, Mizumoto K, et al. Centrosome abnormalities in human carcinomas ofthe gallbladder and intrahepatic and extrahepatic bile ducts. Hepatology,2000,31(1):59-64
[62] Gustafson L M, Gleich L L, Fukasawa K, et al. Centrosome hyperamplification in head andneck squamous cell carcinoma: a potential phenotypic marker of tumor aggressiveness.Laryngoscope,2000,110(11):1798-1801
[63] Carroll P E, Okuda M, Horn H F, et al. Centrosome hyperamplification in human cancer:chromosome instability induced by p53mutation and/or Mdm2overexpression. Oncogene,1999,18(11):1935-1944
[64] Sluder G, Hinchcliffe E H. The coordination of centrosome reproduction with nuclearevents during the cell cycle. Curr Top Dev Biol,2000,49:267-289
[65] Duensing S, Munger K. Human papillomaviruses and centrosome duplication errors:modeling the origins of genomic instability. Oncogene,2002,21(40):6241-6248
[66] Ghadimi B M, Sackett D L, Difilippantonio M J, et al. Centrosome amplification andinstability occurs exclusively in aneuploid, but not in diploid colorectal cancer cell lines,and correlates with numerical chromosomal aberrations. Genes Chromosomes Cancer,2000,27(2):183-190
[67] Lingle W L, Barrett S L, Negron V C, et al. Centrosome amplification drives chromosomalinstability in breast tumor development. Proc Natl Acad Sci U S A,2002,99(4):1978-1983
[68] Pihan G A, Wallace J, Zhou Y, et al. Centrosome abnormalities and chromosome instabilityoccur together in pre-invasive carcinomas. Cancer Res,2003,63(6):1398-1404
[69] Gergely F, Karlsson C, Still I, et al. The TACC domain identifies a family of centrosomalproteins that can interact with microtubules. Proc Natl Acad Sci U S A,2000,97(26):14352-14357
[70] Mayor T, Hacker U, Stierhof Y D, et al. The mechanism regulating the dissociation of thecentrosomal protein C-Nap1from mitotic spindle poles. J Cell Sci,2002,115(Pt16):3275-3284
[71] Ohta T, Essner R, Ryu J H, et al. Characterization of Cep135, a novel coiled-coilcentrosomal protein involved in microtubule organization in mammalian cells. J Cell Biol,2002,156(1):87-99
[72] Purohit A, Tynan S H, Vallee R, et al. Direct interaction of pericentrin with cytoplasmicdynein light intermediate chain contributes to mitotic spindle organization. J Cell Biol,1999,147(3):481-492
[73] Mitelman F. Recurrent chromosome aberrations in cancer. Mutat Res,2000,462(2-3):247-253
[74] Ried T, Heselmeyer-Haddad K, Blegen H, et al. Genomic changes defining the genesis,progression, and malignancy potential in solid human tumors: a phenotype/genotypecorrelation. Genes Chromosomes Cancer,1999,25(3):195-204
[75] Nigg E A. Centrosome aberrations: cause or consequence of cancer progression? Nat RevCancer,2002,2(11):815-825
[76] Millband D N, Campbell L, Hardwick K G. The awesome power of multiple model systems:interpreting the complex nature of spindle checkpoint signaling. Trends Cell Biol,2002,12(5):205-209
[77] Afzelius B A. A human syndrome caused by immotile cilia. Science,1976,193(4250):317-319
[78] Badano J L, Teslovich T M, Katsanis N. The centrosome in human genetic disease. Nat RevGenet,2005,6(3):194-205
[79] Nachury M V, Loktev A V, Zhang Q, et al. A core complex of BBS proteins cooperates withthe GTPase Rab8to promote ciliary membrane biogenesis. Cell,2007,129(6):1201-1213
[80] Pazour G J, Dickert B L, Vucica Y, et al. Chlamydomonas IFT88and its mouse homologue,polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J CellBiol,2000,151(3):709-718
[81] Blacque O E, Leroux M R. Bardet-Biedl syndrome: an emerging pathomechanism ofintracellular transport. Cell Mol Life Sci,2006,63(18):2145-2161
[82] Nonaka S, Yoshiba S, Watanabe D, et al. De novo formation of left-right asymmetry byposterior tilt of nodal cilia. PLoS Biol,2005,3(8): e268
[83] Higginbotham H R, Gleeson J G. The centrosome in neuronal development. TrendsNeurosci,2007,30(6):276-283
[84] Bond J, Roberts E, Springell K, et al. A centrosomal mechanism involving CDK5RAP2andCENPJ controls brain size. Nat Genet,2005,37(4):353-355
[85] Kumar A, Girimaji S C, Duvvari M R, et al. Mutations in STIL, encoding a pericentriolarand centrosomal protein, cause primary microcephaly. Am J Hum Genet,2009,84(2):286-290
[86] Brunk K, Vernay B, Griffith E, et al. Microcephalin coordinates mitosis in the syncytialDrosophila embryo. J Cell Sci,2007,120(Pt20):3578-3588
[87] Jeffers L J, Coull B J, Stack S J, et al. Distinct BRCT domains in Mcph1/Brit1mediateionizing radiation-induced focus formation and centrosomal localization. Oncogene,2008,27(1):139-144
[88] Bond J, Roberts E, Mochida G H, et al. ASPM is a major determinant of cerebral corticalsize. Nat Genet,2002,32(2):316-320
[89] Bond J, Woods C G. Cytoskeletal genes regulating brain size. Curr Opin Cell Biol,2006,18(1):95-101
[90] Wang X, Tsai J W, Imai J H, et al. Asymmetric centrosome inheritance maintains neuralprogenitors in the neocortex. Nature,2009,461(7266):947-955
[91] Lucas E P, Raff J W. Maintaining the proper connection between the centrioles and thepericentriolar matrix requires Drosophila centrosomin. J Cell Biol,2007,178(5):725-732
[92] Basto R, Brunk K, Vinadogrova T, et al. Centrosome amplification can initiatetumorigenesis in flies. Cell,2008,133(6):1032-1042
[93] Castellanos E, Dominguez P, Gonzalez C. Centrosome dysfunction in Drosophila neuralstem cells causes tumors that are not due to genome instability. Curr Biol,2008,18(16):1209-1214
[94] Huttner W B, Kosodo Y. Symmetric versus asymmetric cell division during neurogenesis inthe developing vertebrate central nervous system. Curr Opin Cell Biol,2005,17(6):648-657
[95] Tsai J W, Bremner K H, Vallee R B. Dual subcellular roles for LIS1and dynein in radialneuronal migration in live brain tissue. Nat Neurosci,2007,10(8):970-979
[96] Morris S M, Albrecht U, Reiner O, et al. The lissencephaly gene product Lis1, a proteininvolved in neuronal migration, interacts with a nuclear movement protein, NudC. CurrBiol,1998,8(10):603-606
[97] Aumais J P, Tunstead J R, McNeil R S, et al. NudC associates with Lis1and the dyneinmotor at the leading pole of neurons. J Neurosci,2001,21(24): RC187
[98] Niethammer M, Smith D S, Ayala R, et al. NUDEL is a novel Cdk5substrate that associateswith LIS1and cytoplasmic dynein. Neuron,2000,28(3):697-711
[99] Sasaki S, Shionoya A, Ishida M, et al. A LIS1/NUDEL/cytoplasmic dynein heavy chaincomplex in the developing and adult nervous system. Neuron,2000,28(3):681-696
[100] Feng Y, Olson E C, Stukenberg P T, et al. LIS1regulates CNS lamination by interactingwith mNudE, a central component of the centrosome. Neuron,2000,28(3):665-679
[101] Bielas S L, Gleeson J G. Cytoskeletal-associated proteins in the migration of corticalneurons. J Neurobiol,2004,58(1):149-159
[102] Shu T, Ayala R, Nguyen M D, et al. Ndel1operates in a common pathway with LIS1andcytoplasmic dynein to regulate cortical neuronal positioning. Neuron,2004,44(2):263-277
[103] Andersen J S, Wilkinson C J, Mayor T, et al. Proteomic characterization of the humancentrosome by protein correlation profiling. Nature,2003,426(6966):570-574
[104] Toyo-oka K, Shionoya A, Gambello M J, et al.14-3-3epsilon is important for neuronalmigration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. NatGenet,2003,34(3):274-285
[105] Hatten M E. New directions in neuronal migration. Science,2002,297(5587):1660-1663
[106] Rivas R J, Hatten M E. Motility and cytoskeletal organization of migrating cerebellargranule neurons. J Neurosci,1995,15(2):981-989
[107] Tanaka T, Serneo F F, Higgins C, et al. Lis1and doublecortin function with dynein tomediate coupling of the nucleus to the centrosome in neuronal migration. J Cell Biol,2004,165(5):709-721
[108] Sapir T, Horesh D, Caspi M, et al. Doublecortin mutations cluster in evolutionarilyconserved functional domains. Hum Mol Genet,2000,9(5):703-712
[109] Horesh D, Sapir T, Francis F, et al. Doublecortin, a stabilizer of microtubules. Hum MolGenet,1999,8(9):1599-1610
[110] Caspi M, Atlas R, Kantor A, et al. Interaction between LIS1and doublecortin, twolissencephaly gene products. Hum Mol Genet,2000,9(15):2205-2213
[111] Kramer A, Mailand N, Lukas C, et al. Centrosome-associated Chk1prevents prematureactivation of cyclin-B-Cdk1kinase. Nat Cell Biol,2004,6(9):884-891
[112] Schatten H. The mammalian centrosome and its functional significance. Histochem CellBiol,2008,129(6):667-686
[113] Doxsey S. Re-evaluating centrosome function. Nat Rev Mol Cell Biol,2001,2(9):688-698
[114] Bornens M. Centrosome composition and microtubule anchoring mechanisms. Curr OpinCell Biol,2002,14(1):25-34
[115] Blagden S P, Glover D M. Polar expeditions--provisioning the centrosome for mitosis. NatCell Biol,2003,5(6):505-511
[116] Oakley C E, Oakley B R. Identification of gamma-tubulin, a new member of the tubulinsuperfamily encoded by mipA gene of Aspergillus nidulans. Nature,1989,338(6217):662-664
[117] Tulu U S, Rusan N M, Wadsworth P. Peripheral, non-centrosome-associated microtubulescontribute to spindle formation in centrosome-containing cells. Curr Biol,2003,13(21):1894-1899
[118] Pfeiffer D C, Gard D L. Microtubules in Xenopus oocytes are oriented with theirminus-ends towards the cortex. Cell Motil Cytoskeleton,1999,44(1):34-43
[119] Canaday J, Stoppin-Mellet V, Mutterer J, et al. Higher plant cells: gamma-tubulin andmicrotubule nucleation in the absence of centrosomes. Microsc Res Tech,2000,49(5):487-495
[120] Joshi H C, Palacios M J, McNamara L, et al. Gamma-tubulin is a centrosomal proteinrequired for cell cycle-dependent microtubule nucleation. Nature,1992,356(6364):80-83
[121] Tassin A M, Celati C, Moudjou M, et al. Characterization of the human homologue of theyeast spc98p and its association with gamma-tubulin. J Cell Biol,1998,141(3):689-701
[122] Doxsey S J, Stein P, Evans L, et al. Pericentrin, a highly conserved centrosome proteininvolved in microtubule organization. Cell,1994,76(4):639-650
[123] Flory M R, Davis T N. The centrosomal proteins pericentrin and kendrin are encoded byalternatively spliced products of one gene. Genomics,2003,82(3):401-405
[124] Young A, Dictenberg J B, Purohit A, et al. Cytoplasmic dynein-mediated assembly ofpericentrin and gamma tubulin onto centrosomes. Mol Biol Cell,2000,11(6):2047-2056
[125] Gillingham A K, Munro S. The PACT domain, a conserved centrosomal targeting motif inthe coiled-coil proteins AKAP450and pericentrin. EMBO Rep,2000,1(6):524-529
[126] Martinez-Campos M, Basto R, Baker J, et al. The Drosophila pericentrin-like protein isessential for cilia/flagella function, but appears to be dispensable for mitosis. J Cell Biol,2004,165(5):673-683
[127] Griffith E, Walker S, Martin C A, et al. Mutations in pericentrin cause Seckel syndromewith defective ATR-dependent DNA damage signaling. Nat Genet,2008,40(2):232-236
[128] Tibelius A, Marhold J, Zentgraf H, et al. Microcephalin and pericentrin regulate mitoticentry via centrosome-associated Chk1. J Cell Biol,2009,185(7):1149-1157
[129] Rauch A, Thiel C T, Schindler D, et al. Mutations in the pericentrin (PCNT) gene causeprimordial dwarfism. Science,2008,319(5864):816-819
[130] Basto R, Lau J, Vinogradova T, et al. Flies without centrioles. Cell,2006,125(7):1375-1386
[131] Pihan G, Doxsey S J. Mutations and aneuploidy: co-conspirators in cancer? Cancer Cell,2003,4(2):89-94
[132] Miyoshi K, Asanuma M, Miyazaki I, et al. DISC1localizes to the centrosome by binding tokendrin. Biochem Biophys Res Commun,2004,317(4):1195-1199
[133] Shimizu S, Matsuzaki S, Hattori T, et al. DISC1-kendrin interaction is involved incentrosomal microtubule network formation. Biochem Biophys Res Commun,2008,377(4):1051-1056
[134] Hennah W, Thomson P, Peltonen L, et al. Genes and schizophrenia: beyond schizophrenia:the role of DISC1in major mental illness. Schizophr Bull,2006,32(3):409-416
[135] Kockelkorn T T, Arai M, Matsumoto H, et al. Association study of polymorphisms in the5'upstream region of human DISC1gene with schizophrenia. Neurosci Lett,2004,368(1):41-45
[136] Hildebrandt F, Otto E. Cilia and centrosomes: a unifying pathogenic concept for cystickidney disease? Nat Rev Genet,2005,6(12):928-940
[137] Fischer E, Legue E, Doyen A, et al. Defective planar cell polarity in polycystic kidneydisease. Nat Genet,2006,38(1):21-23
[138] Jonassen J A, San Agustin J, Follit J A, et al. Deletion of IFT20in the mouse kidney causesmisorientation of the mitotic spindle and cystic kidney disease. J Cell Biol,2008,183(3):377-384
[139] Patel V, Li L, Cobo-Stark P, et al. Acute kidney injury and aberrant planar cell polarityinduce cyst formation in mice lacking renal cilia. Hum Mol Genet,2008,17(11):1578-1590
[140] Saburi S, Hester I, Fischer E, et al. Loss of Fat4disrupts PCP signaling and oriented celldivision and leads to cystic kidney disease. Nat Genet,2008,40(8):1010-1015
[141] Mogensen M M, Malik A, Piel M, et al. Microtubule minus-end anchorage at centrosomaland non-centrosomal sites: the role of ninein. J Cell Sci,2000,113(Pt17):3013-3023
[142] Abal M, Piel M, Bouckson-Castaing V, et al. Microtubule release from the centrosome inmigrating cells. J Cell Biol,2002,159(5):731-737
[143] Matsumoto T, Schiller P, Dieterich L C, et al. Ninein is expressed in the cytoplasm ofangiogenic tip-cells and regulates tubular morphogenesis of endothelial cells. ArteriosclerThromb Vasc Biol,2008,28(12):2123-2130
[144] Bautch V L. Ninein leads the way in vessel sprouting. Arterioscler Thromb Vasc Biol,2008,28(12):2094-2095
[145] Kalluri R. Basement membranes: structure, assembly and role in tumour angiogenesis. NatRev Cancer,2003,3(6):422-433
[146] Coultas L, Chawengsaksophak K, Rossant J. Endothelial cells and VEGF in vasculardevelopment. Nature,2005,438(7070):937-945
[147] Carmeliet P. Angiogenesis in life, disease and medicine. Nature,2005,438(7070):932-936
[148] Alitalo K, Tammela T, Petrova T V. Lymphangiogenesis in development and human disease.Nature,2005,438(7070):946-953
[149] Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer,2002,2(10):727-739
[150] Bergers G, Benjamin L E. Tumorigenesis and the angiogenic switch. Nat Rev Cancer,2003,3(6):401-410
[151] Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med,2000,6(4):389-395
[152] Hu Y L, Tee M K, Goetzl E J, et al. Lysophosphatidic acid induction of vascular endothelialgrowth factor expression in human ovarian cancer cells. J Natl Cancer Inst,2001,93(10):762-768
[153] Volpert O V, Stellmach V, Bouck N. The modulation of thrombospondin and other naturallyoccurring inhibitors of angiogenesis during tumor progression. Breast Cancer Res Treat,1995,36(2):119-126
[154] O'Reilly M S. Angiostatin: an endogenous inhibitor of angiogenesis and of tumor growth.EXS,1997,79:273-294
[155] O'Reilly M S, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesisand tumor growth. Cell,1997,88(2):277-285
[156] Folkman J, D'Amore P A. Blood vessel formation: what is its molecular basis? Cell,1996,87(7):1153-1155
[157] Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med,1995,1(1):27-31
[158] Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression.Nat Rev Cancer,2002,2(3):161-174
[159] Folkman J, Beckner K. Angiogenesis imaging. Acad Radiol,2000,7(10):783-785
[160] Gerhardt H, Betsholtz C. Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res,2003,314(1):15-23
[161]Howe A K. Regulation of actin-based cell migration by cAMP/PKA. Biochim Biophys Acta,2004,1692(2-3):159-174
[162] Lauffenburger D A. Cell motility. Making connections count. Nature,1996,383(6599):390-391
[163] Lauffenburger D A, Horwitz A F. Cell migration: a physically integrated molecular process.Cell,1996,84(3):359-369
[164] Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res,2007,100(6):782-794
[165] Machesky L M, Hall A. Rho: a connection between membrane receptor signalling and thecytoskeleton. Trends Cell Biol,1996,6(8):304-310
[166] Sepp K J, Auld V J. RhoA and Rac1GTPases mediate the dynamic rearrangement of actinin peripheral glia. Development,2003,130(9):1825-1835
[167] Takai Y, Sasaki T, Tanaka K, et al. Rho as a regulator of the cytoskeleton. Trends BiochemSci,1995,20(6):227-231
[168] Wittmann T, Waterman-Storer C M. Cell motility: can Rho GTPases and microtubules pointthe way? J Cell Sci,2001,114(Pt21):3795-3803
[169] Xu N, Keung B, Myat M M. Rho GTPase controls invagination and cohesive migration ofthe Drosophila salivary gland through Crumbs and Rho-kinase. Dev Biol,2008,321(1):88-100
[170]Luna E J, Hitt A L. Cytoskeleton--plasma membrane interactions. Science,1992,258(5084):955-964
[171] Malliri A, Collard J G. Role of Rho-family proteins in cell adhesion and cancer. Curr OpinCell Biol,2003,15(5):583-589
[172] Sanz-Moreno V, Gadea G, Ahn J, et al. Rac activation and inactivation control plasticity oftumor cell movement. Cell,2008,135(3):510-523
[173] Soga N, Connolly J O, Chellaiah M, et al. Rac regulates vascular endothelial growth factorstimulated motility. Cell Commun Adhes,2001,8(1):1-13
[174] ten Klooster J P, Leeuwen I, Scheres N, et al. Rac1-induced cell migration requiresmembrane recruitment of the nuclear oncogene SET. EMBO J,2007,26(2):336-345
[175] Bompard G, Caron E. Regulation of WASP/WAVE proteins: making a long story short. JCell Biol,2004,166(7):957-962
[176] Noritake J, Watanabe T, Sato K, et al. IQGAP1: a key regulator of adhesion and migration.J Cell Sci,2005,118(Pt10):2085-2092
[177] Lamalice L, Houle F, Jourdan G, et al. Phosphorylation of tyrosine1214on VEGFR2isrequired for VEGF-induced activation of Cdc42upstream of SAPK2/p38. Oncogene,2004,23(2):434-445
[178] Yamazaki D, Suetsugu S, Miki H, et al. WAVE2is required for directed cell migration andcardiovascular development. Nature,2003,424(6947):452-456
[179] Higashida C, Miyoshi T, Fujita A, et al. Actin polymerization-driven molecular movementof mDia1in living cells. Science,2004,303(5666):2007-2010
[180] Kurokawa K, Matsuda M. Localized RhoA activation as a requirement for the induction ofmembrane ruffling. Mol Biol Cell,2005,16(9):4294-4303
[181] van Nieuw Amerongen G P, Koolwijk P, Versteilen A, et al. Involvement of RhoA/Rhokinase signaling in VEGF-induced endothelial cell migration and angiogenesis in vitro.Arterioscler Thromb Vasc Biol,2003,23(2):211-217
[182] Gingras D, Lamy S, Beliveau R. Tyrosine phosphorylation of the vascularendothelial-growth-factor receptor-2(VEGFR-2) is modulated by Rho proteins. Biochem J,2000,348Pt2:273-280
[183] Rousseau S, Houle F, Huot J. Integrating the VEGF signals leading to actin-based motilityin vascular endothelial cells. Trends Cardiovasc Med,2000,10(8):321-327
[184] Qi J H, Claesson-Welsh L. VEGF-induced activation of phosphoinositide3-kinase isdependent on focal adhesion kinase. Exp Cell Res,2001,263(1):173-182
[185] Williams M R, Arthur J S, Balendran A, et al. The role of3-phosphoinositide-dependentprotein kinase1in activating AGC kinases defined in embryonic stem cells. Curr Biol,2000,10(8):439-448
[186] Jaffe A B, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol,2005,21:247-269
[187] Watanabe T, Noritake J, Kaibuchi K. Regulation of microtubules in cell migration. TrendsCell Biol,2005,15(2):76-83
[188] Fukata M, Nakagawa M, Kaibuchi K. Roles of Rho-family GTPases in cell polarisation anddirectional migration. Curr Opin Cell Biol,2003,15(5):590-597
[189] Cook T A, Nagasaki T, Gundersen G G. Rho guanosine triphosphatase mediates theselective stabilization of microtubules induced by lysophosphatidic acid. J Cell Biol,1998,141(1):175-185
[190] Infante A S, Stein M S, Zhai Y, et al. Detyrosinated (Glu) microtubules are stabilized by anATP-sensitive plus-end cap. J Cell Sci,2000,113(Pt22):3907-3919
[191] Palazzo A F, Cook T A, Alberts A S, et al. mDia mediates Rho-regulated formation andorientation of stable microtubules. Nat Cell Biol,2001,3(8):723-729
[192] Daub H, Gevaert K, Vandekerckhove J, et al. Rac/Cdc42and p65PAK regulate themicrotubule-destabilizing protein stathmin through phosphorylation at serine16. J BiolChem,2001,276(3):1677-1680
[193] Wittmann T, Bokoch G M, Waterman-Storer C M. Regulation of microtubule destabilizingactivity of Op18/stathmin downstream of Rac1. J Biol Chem,2004,279(7):6196-6203
[194] Schuyler S C, Pellman D. Microtubule "plus-end-tracking proteins": The end is just thebeginning. Cell,2001,105(4):421-424
[195] Galjart N, Perez F. A plus-end raft to control microtubule dynamics and function. Curr OpinCell Biol,2003,15(1):48-53
[196] Fukata M, Watanabe T, Noritake J, et al. Rac1and Cdc42capture microtubules throughIQGAP1and CLIP-170. Cell,2002,109(7):873-885
[197] Watanabe T, Wang S, Noritake J, et al. Interaction with IQGAP1links APC to Rac1, Cdc42,and actin filaments during cell polarization and migration. Dev Cell,2004,7(6):871-883
[198] Bashour A M, Fullerton A T, Hart M J, et al. IQGAP1, a Rac-and Cdc42-binding protein,directly binds and cross-links microfilaments. J Cell Biol,1997,137(7):1555-1566
[199] Bhatt A, Kaverina I, Otey C, et al. Regulation of focal complex composition anddisassembly by the calcium-dependent protease calpain. J Cell Sci,2002,115(Pt17):3415-3425
[200] Hynes R O. Integrins: bidirectional, allosteric signaling machines. Cell,2002,110(6):673-687
[201] Ananthakrishnan R, Ehrlicher A. The forces behind cell movement. Int J Biol Sci,2007,3(5):303-317
[202] Plastino J, Sykes C. The actin slingshot. Curr Opin Cell Biol,2005,17(1):62-66
[203] Raftopoulou M, Hall A. Cell migration: Rho GTPases lead the way. Dev Biol,2004,265(1):23-32
[204] Faix J, Rottner K. The making of filopodia. Curr Opin Cell Biol,2006,18(1):18-25
[205] Etienne-Manneville S. Actin and microtubules in cell motility: which one is in control?Traffic,2004,5(7):470-477
[206] Boudreau N J, Jones P L. Extracellular matrix and integrin signalling: the shape of things tocome. Biochem J,1999,339(Pt3):481-488
[207] Hamadi A, Bouali M, Dontenwill M, et al. Regulation of focal adhesion dynamics anddisassembly by phosphorylation of FAK at tyrosine397. J Cell Sci,2005,118(Pt19):4415-4425
[208] Subauste M C, Pertz O, Adamson E D, et al. Vinculin modulation of paxillin-FAKinteractions regulates ERK to control survival and motility. J Cell Biol,2004,165(3):371-381
[209] Michael K E, Dumbauld D W, Burns K L, et al. Focal adhesion kinase modulates celladhesion strengthening via integrin activation. Mol Biol Cell,2009,20(9):2508-2519
[210] Norgauer J, Krutmann J, Dobos G J, et al. Actin polymerization, calcium-transients, andphospholipid metabolism in human neutrophils after stimulation with interleukin-8andN-formyl peptide. J Invest Dermatol,1994,102(3):310-314
[211] Romer L H, Birukov K G, Garcia J G. Focal adhesions: paradigm for a signaling nexus. CircRes,2006,98(5):606-616
[212] Li J P, Fu Y N, Chen Y R, et al. JNK pathway-associated phosphatase dephosphorylatesfocal adhesion kinase and suppresses cell migration. J Biol Chem,2010,285(8):5472-5478
[213] Kimura K, Ito M, Amano M, et al. Regulation of myosin phosphatase by Rho andRho-associated kinase (Rho-kinase). Science,1996,273(5272):245-248
[214] Feng J, Ito M, Kureishi Y, et al. Rho-associated kinase of chicken gizzard smooth muscle. JBiol Chem,1999,274(6):3744-3752
[215] Riento K, Ridley A J. Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol CellBiol,2003,4(6):446-456
[216] Ramos E, Wysolmerski R B, Masaracchia R A. Myosin phosphorylation by humancdc42-dependent S6/H4kinase/gammaPAK from placenta and lymphoid cells. ReceptSignal Transduct,1997,7(2):99-110
[217] Chew T L, Masaracchia R A, Goeckeler Z M, et al. Phosphorylation of non-muscle myosinII regulatory light chain by p21-activated kinase (gamma-PAK). J Muscle Res Cell Motil,1998,19(8):839-854
[218] Schultz J, Milpetz F, Bork P, et al. SMART, a simple modular architecture research tool:identification of signaling domains. Proc Natl Acad Sci U S A,1998,95(11):5857-5864
[219] Rebhan M, Chalifa-Caspi V, Prilusky J, et al. GeneCards: a novel functional genomicscompendium with automated data mining and query reformulation support. Bioinformatics,1998,14(8):656-664
[220] Glover J N, Harrison S C. Crystal structure of the heterodimeric bZIP transcription factorc-Fos-c-Jun bound to DNA. Nature,1995,373(6511):257-261
[221] Frank S, Schulthess T, Landwehr R, et al. Characterization of the matrilin coiled-coildomains reveals seven novel isoforms. J Biol Chem,2002,277(21):19071-19079
[222] Mason J M, Arndt K M. Coiled coil domains: stability, specificity, and biologicalimplications. Chembiochem,2004,5(2):170-176
[223] Bouckson-Castaing V, Moudjou M, Ferguson D J, et al. Molecular characterisation ofninein, a new coiled-coil protein of the centrosome. J Cell Sci,1996,109(Pt1):179-190
[224] Wilkinson C J, Carl M, Harris W A. Cep70and Cep131contribute to ciliogenesis inzebrafish embryos. BMC Cell Biol,2009,10:17
[225] Ibanez-Tallon I, Heintz N, Omran H. To beat or not to beat: roles of cilia in developmentand disease. Hum Mol Genet,2003,12Spec No1: R27-35
[226] Bisgrove B W, Yost H J. The roles of cilia in developmental disorders and disease.Development,2006,133(21):4131-4143
[227] Scholey J M. Intraflagellar transport motors in cilia: moving along the cell's antenna. J CellBiol,2008,180(1):23-29
[228] Hubbert C, Guardiola A, Shao R, et al. HDAC6is a microtubule-associated deacetylase.Nature,2002,417(6887):455-458
[229] Shiratsuchi G, Kamiya R, Hirono M. Scaffolding function of the Chlamydomonasprocentriole protein CRC70, a member of the conserved Cep70family. J Cell Sci,2011,124(Pt17):2964-2975
[230] Dippell J, Varlam D E. Early sonographic aspects of kidney morphology in Bardet-Biedlsyndrome. Pediatr Nephrol,1998,12(7):559-563
[231]Dutcher S K. Finding treasures in frozen cells: new centriole intermediates. Bioessays,2007,29(7):630-634
[232] Nakazawa Y, Hiraki M, Kamiya R, et al. SAS-6is a cartwheel protein that establishes the9-fold symmetry of the centriole. Curr Biol,2007,17(24):2169-2174
[233] Matsuura K, Lefebvre P A, Kamiya R, et al. Bld10p, a novel protein essential for basalbody assembly in Chlamydomonas: localization to the cartwheel, the first ninefoldsymmetrical structure appearing during assembly. J Cell Biol,2004,165(5):663-671
[234] Hiraki M, Nakazawa Y, Kamiya R, et al. Bld10p constitutes the cartwheel-spoke tip andstabilizes the9-fold symmetry of the centriole. Curr Biol,2007,17(20):1778-1783
[235] Zhou J, Panda D, Landen J W, et al. Minor alteration of microtubule dynamics causes lossof tension across kinetochore pairs and activates the spindle checkpoint. J Biol Chem,2002,277(19):17200-17208
[236] Delaval B, Doxsey S J. Pericentrin in cellular function and disease. J Cell Biol,2010,188(2):181-190
[237] Kardon J R, Vale R D. Regulators of the cytoplasmic dynein motor. Nat Rev Mol Cell Biol,2009,10(12):854-865
[238] Wade R H. On and around microtubules: an overview. Mol Biotechnol,2009,43(2):177-191
[239] Schiebel E. gamma-tubulin complexes: binding to the centrosome, regulation andmicrotubule nucleation. Curr Opin Cell Biol,2000,12(1):113-118
[240] van der Vaart B, Akhmanova A, Straube A. Regulation of microtubule dynamic instability.Biochem Soc Trans,2009,37(Pt5):1007-1013
[241] Sun X, Shi X, Liu M, et al. Mdp3is a novel microtubule-binding protein that regulatesmicrotubule assembly and stability. Cell Cycle,2011,10(22):3929-3937
[242] Tanenbaum M E, Medema R H. Mechanisms of centrosome separation and bipolar spindleassembly. Dev Cell,2010,19(6):797-806
[243] Siller K H, Doe C Q. Spindle orientation during asymmetric cell division. Nat Cell Biol,2009,11(4):365-374
[244] Pease J C, Tirnauer J S. Mitotic spindle misorientation in cancer--out of alignment and intothe fire. J Cell Sci,2011,124(Pt7):1007-1016
[245] Thompson S L, Bakhoum S F, Compton D A. Mechanisms of chromosomal instability. CurrBiol,2010,20(6): R285-295
[246] Taylor S M, Nevis K R, Park H L, et al. Angiogenic factor signaling regulates centrosomeduplication in endothelial cells of developing blood vessels. Blood,2010,116(16):3108-3117
[247] Shi X, Sun X, Liu M, et al. CEP70protein interacts with gamma-tubulin to localize at thecentrosome and is critical for mitotic spindle assembly. J Biol Chem,2011,286(38):33401-33408
[248] Shi X, Wang J, Yang Y, et al. Cep70promotes microtubule assembly in vitro by increasingmicrotubule elongation. Acta Biochim Biophys Sin (Shanghai),2012,44(5):450-454
[249] Gao J, Sun L, Huo L, et al. CYLD regulates angiogenesis by mediating vascular endothelialcell migration. Blood,2010,115(20):4130-4137
[250] Li D, Xie S, Ren Y, et al. Microtubule-associated deacetylase HDAC6promotesangiogenesis by regulating cell migration in an EB1-dependent manner. Protein Cell,2011,2(2):150-160
[251] Gotlieb A I. The endothelial cytoskeleton: organization in normal and regeneratingendothelium. Toxicol Pathol,1990,18(4Pt1):603-617
[252] Ren X D, Kiosses W B, Schwartz M A. Regulation of the small GTP-binding protein Rhoby cell adhesion and the cytoskeleton. EMBO J,1999,18(3):578-585
[2] Dictenberg J B, Zimmerman W, Sparks C A, et al. Pericentrin and gamma-tubulin form aprotein complex and are organized into a novel lattice at the centrosome. J Cell Biol,1998,141(1):163-174
[3] Dammermann A, Merdes A. Assembly of centrosomal proteins and microtubuleorganization depends on PCM-1. J Cell Biol,2002,159(2):255-266
[4] Moritz M, Braunfeld M B, Sedat J W, et al. Microtubule nucleation bygamma-tubulin-containing rings in the centrosome. Nature,1995,378(6557):638-640
[5] Delgehyr N, Sillibourne J, Bornens M. Microtubule nucleation and anchoring at thecentrosome are independent processes linked by ninein function. J Cell Sci,2005,118(Pt8):1565-1575
[6] Louie R K, Bahmanyar S, Siemers K A, et al. Adenomatous polyposis coli and EB1localizein close proximity of the mother centriole and EB1is a functional component ofcentrosomes. J Cell Sci,2004,117(Pt7):1117-1128
[7] Yan X, Habedanck R, Nigg E A. A complex of two centrosomal proteins, CAP350and FOP,cooperates with EB1in microtubule anchoring. Mol Biol Cell,2006,17(2):634-644
[8] Guo J, Yang Z, Song W, et al. Nudel contributes to microtubule anchoring at the mothercentriole and is involved in both dynein-dependent and-independent centrosomal proteinassembly. Mol Biol Cell,2006,17(2):680-689
[9] Taylor S, Peters J M. Polo and Aurora kinases: lessons derived from chemical biology. CurrOpin Cell Biol,2008,20(1):77-84
[10] Bettencourt-Dias M, Glover D M. Centrosome biogenesis and function: centrosomicsbrings new understanding. Nat Rev Mol Cell Biol,2007,8(6):451-463
[11] Tokuyama Y, Horn H F, Kawamura K, et al. Specific phosphorylation of nucleophosmin onThr(199) by cyclin-dependent kinase2-cyclin E and its role in centrosome duplication. JBiol Chem,2001,276(24):21529-21537
[12] Okuda M. The role of nucleophosmin in centrosome duplication. Oncogene,2002,21(40):6170-6174
[13] Chen Z, Indjeian V B, McManus M, et al. CP110, a cell cycle-dependent CDK substrate,regulates centrosome duplication in human cells. Dev Cell,2002,3(3):339-350
[14] Geng Y, Lee Y M, Welcker M, et al. Kinase-independent function of cyclin E. Mol Cell,2007,25(1):127-139
[15] Ferguson R L, Maller J L. Cyclin E-dependent localization of MCM5regulates centrosomeduplication. J Cell Sci,2008,121(Pt19):3224-3232
[16] Hemerly A S, Prasanth S G, Siddiqui K, et al. Orc1controls centriole and centrosome copynumber in human cells. Science,2009,323(5915):789-793
[17] Habedanck R, Stierhof Y D, Wilkinson C J, et al. The Polo kinase Plk4functions incentriole duplication. Nat Cell Biol,2005,7(11):1140-1146
[18] Loncarek J, Hergert P, Magidson V, et al. Control of daughter centriole formation by thepericentriolar material. Nat Cell Biol,2008,10(3):322-328
[19] Vladar E K, Stearns T. Molecular characterization of centriole assembly in ciliatedepithelial cells. J Cell Biol,2007,178(1):31-42
[20] Khodjakov A, Rieder C L, Sluder G, et al. De novo formation of centrosomes in vertebratecells arrested during S phase. J Cell Biol,2002,158(7):1171-1181
[21] Haren L, Remy M H, Bazin I, et al. NEDD1-dependent recruitment of the gamma-tubulinring complex to the centrosome is necessary for centriole duplication and spindle assembly.J Cell Biol,2006,172(4):505-515
[22] Zhu F, Lawo S, Bird A, et al. The mammalian SPD-2ortholog Cep192regulatescentrosome biogenesis. Curr Biol,2008,18(2):136-141
[23] O'Toole E T, Giddings T H, McIntosh J R, et al. Three-dimensional organization of basalbodies from wild-type and delta-tubulin deletion strains of Chlamydomonas reinhardtii.Mol Biol Cell,2003,14(7):2999-3012
[24] Pelletier L, O'Toole E, Schwager A, et al. Centriole assembly in Caenorhabditis elegans.Nature,2006,444(7119):619-623
[25] Dutcher S K, Morrissette N S, Preble A M, et al. Epsilon-tubulin is an essential componentof the centriole. Mol Biol Cell,2002,13(11):3859-3869
[26] Strnad P, Leidel S, Vinogradova T, et al. Regulated HsSAS-6levels ensure formation of asingle procentriole per centriole during the centrosome duplication cycle. Dev Cell,2007,13(2):203-213
[27] Zyss D, Gergely F. Centrosome function in cancer: guilty or innocent? Trends Cell Biol,2009,19(7):334-346
[28] Doxsey S, Zimmerman W, Mikule K. Centrosome control of the cell cycle. Trends Cell Biol,2005,15(6):303-311
[29] Neben K, Tews B, Wrobel G, et al. Gene expression patterns in acute myeloid leukemiacorrelate with centrosome aberrations and numerical chromosome changes. Oncogene,2004,23(13):2379-2384
[30] Matsumoto Y, Maller J L. A centrosomal localization signal in cyclin E required forCdk2-independent S phase entry. Science,2004,306(5697):885-888
[31] Luders J, Stearns T. Microtubule-organizing centres: a re-evaluation. Nat Rev Mol Cell Biol,2007,8(2):161-167
[32] O'Connell C B, Khodjakov A L. Cooperative mechanisms of mitotic spindle formation. JCell Sci,2007,120(Pt10):1717-1722
[33] Rebollo E, Sampaio P, Januschke J, et al. Functionally unequal centrosomes drive spindleorientation in asymmetrically dividing Drosophila neural stem cells. Dev Cell,2007,12(3):467-474
[34] Rusan N M, Peifer M. A role for a novel centrosome cycle in asymmetric cell division. JCell Biol,2007,177(1):13-20
[35] Toyoshima F, Nishida E. Integrin-mediated adhesion orients the spindle parallel to thesubstratum in an EB1-and myosin X-dependent manner. EMBO J,2007,26(6):1487-1498
[36] Yamashita Y M, Mahowald A P, Perlin J R, et al. Asymmetric inheritance of mother versusdaughter centrosome in stem cell division. Science,2007,315(5811):518-521
[37] Rieder C L, Faruki S, Khodjakov A. The centrosome in vertebrates: more than amicrotubule-organizing center. Trends Cell Biol,2001,11(10):413-419
[38] Desai A, Mitchison T J. Microtubule polymerization dynamics. Annu Rev Cell Dev Biol,1997,13:83-117
[39] Nogales E, Wolf S G, Downing K H. Structure of the alpha beta tubulin dimer by electroncrystallography. Nature,1998,391(6663):199-203
[40] Lowe J, Li H, Downing K H, et al. Refined structure of alpha beta-tubulin at3.5Aresolution. J Mol Biol,2001,313(5):1045-1057
[41] Tuszynski J A, Carpenter E J, Huzil J T, et al. The evolution of the structure of tubulin andits potential consequences for the role and function of microtubules in cells and embryos.Int J Dev Biol,2006,50(2-3):341-358
[42] Conde C, Caceres A. Microtubule assembly, organization and dynamics in axons anddendrites. Nat Rev Neurosci,2009,10(5):319-332
[43] Westermann S, Weber K. Post-translational modifications regulate microtubule function.Nat Rev Mol Cell Biol,2003,4(12):938-947
[44] Mostowy S, Cossart P. Septins: the fourth component of the cytoskeleton. Nat Rev Mol CellBiol,2012,13(3):183-194
[45] Zheng Y, Wong M L, Alberts B, et al. Nucleation of microtubule assembly by agamma-tubulin-containing ring complex. Nature,1995,378(6557):578-583
[46] Gunawardane R N, Martin O C, Cao K, et al. Characterization and reconstitution ofDrosophila gamma-tubulin ring complex subunits. J Cell Biol,2000,151(7):1513-1524
[47] Murphy S M, Preble A M, Patel U K, et al. GCP5and GCP6: two new members of thehuman gamma-tubulin complex. Mol Biol Cell,2001,12(11):3340-3352
[48] Murphy S M, Urbani L, Stearns T. The mammalian gamma-tubulin complex containshomologues of the yeast spindle pole body components spc97p and spc98p. J Cell Biol,1998,141(3):663-674
[49] Teixido-Travesa N, Villen J, Lacasa C, et al. The gammaTuRC revisited: a comparativeanalysis of interphase and mitotic human gammaTuRC redefines the set of core componentsand identifies the novel subunit GCP8. Mol Biol Cell,2010,21(22):3963-3972
[50] Hutchins J R, Toyoda Y, Hegemann B, et al. Systematic analysis of human proteincomplexes identifies chromosome segregation proteins. Science,2010,328(5978):593-599
[51] Oegema K, Wiese C, Martin O C, et al. Characterization of two related Drosophilagamma-tubulin complexes that differ in their ability to nucleate microtubules. J Cell Biol,1999,144(4):721-733
[52] Kollman J M, Merdes A, Mourey L, et al. Microtubule nucleation by gamma-tubulincomplexes. Nat Rev Mol Cell Biol,2011,12(11):709-721
[53] Nigg E A, Raff J W. Centrioles, centrosomes, and cilia in health and disease. Cell,2009,139(4):663-678
[54] Lingle W L, Lutz W H, Ingle J N, et al. Centrosome hypertrophy in human breast tumors:implications for genomic stability and cell polarity. Proc Natl Acad Sci U S A,1998,95(6):2950-2955
[55] Pihan G A, Purohit A, Wallace J, et al. Centrosome defects and genetic instability inmalignant tumors. Cancer Res,1998,58(17):3974-3985
[56] Weber R G, Bridger J M, Benner A, et al. Centrosome amplification as a possiblemechanism for numerical chromosome aberrations in cerebral primitive neuroectodermaltumors with TP53mutations. Cytogenet Cell Genet,1998,83(3-4):266-269
[57] Pihan G A, Purohit A, Wallace J, et al. Centrosome defects can account for cellular andgenetic changes that characterize prostate cancer progression. Cancer Res,2001,61(5):2212-2219
[58] Lingle W L, Salisbury J L. Altered centrosome structure is associated with abnormalmitoses in human breast tumors. Am J Pathol,1999,155(6):1941-1951
[59] Sato N, Mizumoto K, Nakamura M, et al. Centrosome abnormalities in pancreatic ductalcarcinoma. Clin Cancer Res,1999,5(5):963-970
[60] Sato N, Mizumoto K, Nakamura M, et al. Correlation between centrosome abnormalitiesand chromosomal instability in human pancreatic cancer cells. Cancer Genet Cytogenet,2001,126(1):13-19
[61] Kuo K K, Sato N, Mizumoto K, et al. Centrosome abnormalities in human carcinomas ofthe gallbladder and intrahepatic and extrahepatic bile ducts. Hepatology,2000,31(1):59-64
[62] Gustafson L M, Gleich L L, Fukasawa K, et al. Centrosome hyperamplification in head andneck squamous cell carcinoma: a potential phenotypic marker of tumor aggressiveness.Laryngoscope,2000,110(11):1798-1801
[63] Carroll P E, Okuda M, Horn H F, et al. Centrosome hyperamplification in human cancer:chromosome instability induced by p53mutation and/or Mdm2overexpression. Oncogene,1999,18(11):1935-1944
[64] Sluder G, Hinchcliffe E H. The coordination of centrosome reproduction with nuclearevents during the cell cycle. Curr Top Dev Biol,2000,49:267-289
[65] Duensing S, Munger K. Human papillomaviruses and centrosome duplication errors:modeling the origins of genomic instability. Oncogene,2002,21(40):6241-6248
[66] Ghadimi B M, Sackett D L, Difilippantonio M J, et al. Centrosome amplification andinstability occurs exclusively in aneuploid, but not in diploid colorectal cancer cell lines,and correlates with numerical chromosomal aberrations. Genes Chromosomes Cancer,2000,27(2):183-190
[67] Lingle W L, Barrett S L, Negron V C, et al. Centrosome amplification drives chromosomalinstability in breast tumor development. Proc Natl Acad Sci U S A,2002,99(4):1978-1983
[68] Pihan G A, Wallace J, Zhou Y, et al. Centrosome abnormalities and chromosome instabilityoccur together in pre-invasive carcinomas. Cancer Res,2003,63(6):1398-1404
[69] Gergely F, Karlsson C, Still I, et al. The TACC domain identifies a family of centrosomalproteins that can interact with microtubules. Proc Natl Acad Sci U S A,2000,97(26):14352-14357
[70] Mayor T, Hacker U, Stierhof Y D, et al. The mechanism regulating the dissociation of thecentrosomal protein C-Nap1from mitotic spindle poles. J Cell Sci,2002,115(Pt16):3275-3284
[71] Ohta T, Essner R, Ryu J H, et al. Characterization of Cep135, a novel coiled-coilcentrosomal protein involved in microtubule organization in mammalian cells. J Cell Biol,2002,156(1):87-99
[72] Purohit A, Tynan S H, Vallee R, et al. Direct interaction of pericentrin with cytoplasmicdynein light intermediate chain contributes to mitotic spindle organization. J Cell Biol,1999,147(3):481-492
[73] Mitelman F. Recurrent chromosome aberrations in cancer. Mutat Res,2000,462(2-3):247-253
[74] Ried T, Heselmeyer-Haddad K, Blegen H, et al. Genomic changes defining the genesis,progression, and malignancy potential in solid human tumors: a phenotype/genotypecorrelation. Genes Chromosomes Cancer,1999,25(3):195-204
[75] Nigg E A. Centrosome aberrations: cause or consequence of cancer progression? Nat RevCancer,2002,2(11):815-825
[76] Millband D N, Campbell L, Hardwick K G. The awesome power of multiple model systems:interpreting the complex nature of spindle checkpoint signaling. Trends Cell Biol,2002,12(5):205-209
[77] Afzelius B A. A human syndrome caused by immotile cilia. Science,1976,193(4250):317-319
[78] Badano J L, Teslovich T M, Katsanis N. The centrosome in human genetic disease. Nat RevGenet,2005,6(3):194-205
[79] Nachury M V, Loktev A V, Zhang Q, et al. A core complex of BBS proteins cooperates withthe GTPase Rab8to promote ciliary membrane biogenesis. Cell,2007,129(6):1201-1213
[80] Pazour G J, Dickert B L, Vucica Y, et al. Chlamydomonas IFT88and its mouse homologue,polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J CellBiol,2000,151(3):709-718
[81] Blacque O E, Leroux M R. Bardet-Biedl syndrome: an emerging pathomechanism ofintracellular transport. Cell Mol Life Sci,2006,63(18):2145-2161
[82] Nonaka S, Yoshiba S, Watanabe D, et al. De novo formation of left-right asymmetry byposterior tilt of nodal cilia. PLoS Biol,2005,3(8): e268
[83] Higginbotham H R, Gleeson J G. The centrosome in neuronal development. TrendsNeurosci,2007,30(6):276-283
[84] Bond J, Roberts E, Springell K, et al. A centrosomal mechanism involving CDK5RAP2andCENPJ controls brain size. Nat Genet,2005,37(4):353-355
[85] Kumar A, Girimaji S C, Duvvari M R, et al. Mutations in STIL, encoding a pericentriolarand centrosomal protein, cause primary microcephaly. Am J Hum Genet,2009,84(2):286-290
[86] Brunk K, Vernay B, Griffith E, et al. Microcephalin coordinates mitosis in the syncytialDrosophila embryo. J Cell Sci,2007,120(Pt20):3578-3588
[87] Jeffers L J, Coull B J, Stack S J, et al. Distinct BRCT domains in Mcph1/Brit1mediateionizing radiation-induced focus formation and centrosomal localization. Oncogene,2008,27(1):139-144
[88] Bond J, Roberts E, Mochida G H, et al. ASPM is a major determinant of cerebral corticalsize. Nat Genet,2002,32(2):316-320
[89] Bond J, Woods C G. Cytoskeletal genes regulating brain size. Curr Opin Cell Biol,2006,18(1):95-101
[90] Wang X, Tsai J W, Imai J H, et al. Asymmetric centrosome inheritance maintains neuralprogenitors in the neocortex. Nature,2009,461(7266):947-955
[91] Lucas E P, Raff J W. Maintaining the proper connection between the centrioles and thepericentriolar matrix requires Drosophila centrosomin. J Cell Biol,2007,178(5):725-732
[92] Basto R, Brunk K, Vinadogrova T, et al. Centrosome amplification can initiatetumorigenesis in flies. Cell,2008,133(6):1032-1042
[93] Castellanos E, Dominguez P, Gonzalez C. Centrosome dysfunction in Drosophila neuralstem cells causes tumors that are not due to genome instability. Curr Biol,2008,18(16):1209-1214
[94] Huttner W B, Kosodo Y. Symmetric versus asymmetric cell division during neurogenesis inthe developing vertebrate central nervous system. Curr Opin Cell Biol,2005,17(6):648-657
[95] Tsai J W, Bremner K H, Vallee R B. Dual subcellular roles for LIS1and dynein in radialneuronal migration in live brain tissue. Nat Neurosci,2007,10(8):970-979
[96] Morris S M, Albrecht U, Reiner O, et al. The lissencephaly gene product Lis1, a proteininvolved in neuronal migration, interacts with a nuclear movement protein, NudC. CurrBiol,1998,8(10):603-606
[97] Aumais J P, Tunstead J R, McNeil R S, et al. NudC associates with Lis1and the dyneinmotor at the leading pole of neurons. J Neurosci,2001,21(24): RC187
[98] Niethammer M, Smith D S, Ayala R, et al. NUDEL is a novel Cdk5substrate that associateswith LIS1and cytoplasmic dynein. Neuron,2000,28(3):697-711
[99] Sasaki S, Shionoya A, Ishida M, et al. A LIS1/NUDEL/cytoplasmic dynein heavy chaincomplex in the developing and adult nervous system. Neuron,2000,28(3):681-696
[100] Feng Y, Olson E C, Stukenberg P T, et al. LIS1regulates CNS lamination by interactingwith mNudE, a central component of the centrosome. Neuron,2000,28(3):665-679
[101] Bielas S L, Gleeson J G. Cytoskeletal-associated proteins in the migration of corticalneurons. J Neurobiol,2004,58(1):149-159
[102] Shu T, Ayala R, Nguyen M D, et al. Ndel1operates in a common pathway with LIS1andcytoplasmic dynein to regulate cortical neuronal positioning. Neuron,2004,44(2):263-277
[103] Andersen J S, Wilkinson C J, Mayor T, et al. Proteomic characterization of the humancentrosome by protein correlation profiling. Nature,2003,426(6966):570-574
[104] Toyo-oka K, Shionoya A, Gambello M J, et al.14-3-3epsilon is important for neuronalmigration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. NatGenet,2003,34(3):274-285
[105] Hatten M E. New directions in neuronal migration. Science,2002,297(5587):1660-1663
[106] Rivas R J, Hatten M E. Motility and cytoskeletal organization of migrating cerebellargranule neurons. J Neurosci,1995,15(2):981-989
[107] Tanaka T, Serneo F F, Higgins C, et al. Lis1and doublecortin function with dynein tomediate coupling of the nucleus to the centrosome in neuronal migration. J Cell Biol,2004,165(5):709-721
[108] Sapir T, Horesh D, Caspi M, et al. Doublecortin mutations cluster in evolutionarilyconserved functional domains. Hum Mol Genet,2000,9(5):703-712
[109] Horesh D, Sapir T, Francis F, et al. Doublecortin, a stabilizer of microtubules. Hum MolGenet,1999,8(9):1599-1610
[110] Caspi M, Atlas R, Kantor A, et al. Interaction between LIS1and doublecortin, twolissencephaly gene products. Hum Mol Genet,2000,9(15):2205-2213
[111] Kramer A, Mailand N, Lukas C, et al. Centrosome-associated Chk1prevents prematureactivation of cyclin-B-Cdk1kinase. Nat Cell Biol,2004,6(9):884-891
[112] Schatten H. The mammalian centrosome and its functional significance. Histochem CellBiol,2008,129(6):667-686
[113] Doxsey S. Re-evaluating centrosome function. Nat Rev Mol Cell Biol,2001,2(9):688-698
[114] Bornens M. Centrosome composition and microtubule anchoring mechanisms. Curr OpinCell Biol,2002,14(1):25-34
[115] Blagden S P, Glover D M. Polar expeditions--provisioning the centrosome for mitosis. NatCell Biol,2003,5(6):505-511
[116] Oakley C E, Oakley B R. Identification of gamma-tubulin, a new member of the tubulinsuperfamily encoded by mipA gene of Aspergillus nidulans. Nature,1989,338(6217):662-664
[117] Tulu U S, Rusan N M, Wadsworth P. Peripheral, non-centrosome-associated microtubulescontribute to spindle formation in centrosome-containing cells. Curr Biol,2003,13(21):1894-1899
[118] Pfeiffer D C, Gard D L. Microtubules in Xenopus oocytes are oriented with theirminus-ends towards the cortex. Cell Motil Cytoskeleton,1999,44(1):34-43
[119] Canaday J, Stoppin-Mellet V, Mutterer J, et al. Higher plant cells: gamma-tubulin andmicrotubule nucleation in the absence of centrosomes. Microsc Res Tech,2000,49(5):487-495
[120] Joshi H C, Palacios M J, McNamara L, et al. Gamma-tubulin is a centrosomal proteinrequired for cell cycle-dependent microtubule nucleation. Nature,1992,356(6364):80-83
[121] Tassin A M, Celati C, Moudjou M, et al. Characterization of the human homologue of theyeast spc98p and its association with gamma-tubulin. J Cell Biol,1998,141(3):689-701
[122] Doxsey S J, Stein P, Evans L, et al. Pericentrin, a highly conserved centrosome proteininvolved in microtubule organization. Cell,1994,76(4):639-650
[123] Flory M R, Davis T N. The centrosomal proteins pericentrin and kendrin are encoded byalternatively spliced products of one gene. Genomics,2003,82(3):401-405
[124] Young A, Dictenberg J B, Purohit A, et al. Cytoplasmic dynein-mediated assembly ofpericentrin and gamma tubulin onto centrosomes. Mol Biol Cell,2000,11(6):2047-2056
[125] Gillingham A K, Munro S. The PACT domain, a conserved centrosomal targeting motif inthe coiled-coil proteins AKAP450and pericentrin. EMBO Rep,2000,1(6):524-529
[126] Martinez-Campos M, Basto R, Baker J, et al. The Drosophila pericentrin-like protein isessential for cilia/flagella function, but appears to be dispensable for mitosis. J Cell Biol,2004,165(5):673-683
[127] Griffith E, Walker S, Martin C A, et al. Mutations in pericentrin cause Seckel syndromewith defective ATR-dependent DNA damage signaling. Nat Genet,2008,40(2):232-236
[128] Tibelius A, Marhold J, Zentgraf H, et al. Microcephalin and pericentrin regulate mitoticentry via centrosome-associated Chk1. J Cell Biol,2009,185(7):1149-1157
[129] Rauch A, Thiel C T, Schindler D, et al. Mutations in the pericentrin (PCNT) gene causeprimordial dwarfism. Science,2008,319(5864):816-819
[130] Basto R, Lau J, Vinogradova T, et al. Flies without centrioles. Cell,2006,125(7):1375-1386
[131] Pihan G, Doxsey S J. Mutations and aneuploidy: co-conspirators in cancer? Cancer Cell,2003,4(2):89-94
[132] Miyoshi K, Asanuma M, Miyazaki I, et al. DISC1localizes to the centrosome by binding tokendrin. Biochem Biophys Res Commun,2004,317(4):1195-1199
[133] Shimizu S, Matsuzaki S, Hattori T, et al. DISC1-kendrin interaction is involved incentrosomal microtubule network formation. Biochem Biophys Res Commun,2008,377(4):1051-1056
[134] Hennah W, Thomson P, Peltonen L, et al. Genes and schizophrenia: beyond schizophrenia:the role of DISC1in major mental illness. Schizophr Bull,2006,32(3):409-416
[135] Kockelkorn T T, Arai M, Matsumoto H, et al. Association study of polymorphisms in the5'upstream region of human DISC1gene with schizophrenia. Neurosci Lett,2004,368(1):41-45
[136] Hildebrandt F, Otto E. Cilia and centrosomes: a unifying pathogenic concept for cystickidney disease? Nat Rev Genet,2005,6(12):928-940
[137] Fischer E, Legue E, Doyen A, et al. Defective planar cell polarity in polycystic kidneydisease. Nat Genet,2006,38(1):21-23
[138] Jonassen J A, San Agustin J, Follit J A, et al. Deletion of IFT20in the mouse kidney causesmisorientation of the mitotic spindle and cystic kidney disease. J Cell Biol,2008,183(3):377-384
[139] Patel V, Li L, Cobo-Stark P, et al. Acute kidney injury and aberrant planar cell polarityinduce cyst formation in mice lacking renal cilia. Hum Mol Genet,2008,17(11):1578-1590
[140] Saburi S, Hester I, Fischer E, et al. Loss of Fat4disrupts PCP signaling and oriented celldivision and leads to cystic kidney disease. Nat Genet,2008,40(8):1010-1015
[141] Mogensen M M, Malik A, Piel M, et al. Microtubule minus-end anchorage at centrosomaland non-centrosomal sites: the role of ninein. J Cell Sci,2000,113(Pt17):3013-3023
[142] Abal M, Piel M, Bouckson-Castaing V, et al. Microtubule release from the centrosome inmigrating cells. J Cell Biol,2002,159(5):731-737
[143] Matsumoto T, Schiller P, Dieterich L C, et al. Ninein is expressed in the cytoplasm ofangiogenic tip-cells and regulates tubular morphogenesis of endothelial cells. ArteriosclerThromb Vasc Biol,2008,28(12):2123-2130
[144] Bautch V L. Ninein leads the way in vessel sprouting. Arterioscler Thromb Vasc Biol,2008,28(12):2094-2095
[145] Kalluri R. Basement membranes: structure, assembly and role in tumour angiogenesis. NatRev Cancer,2003,3(6):422-433
[146] Coultas L, Chawengsaksophak K, Rossant J. Endothelial cells and VEGF in vasculardevelopment. Nature,2005,438(7070):937-945
[147] Carmeliet P. Angiogenesis in life, disease and medicine. Nature,2005,438(7070):932-936
[148] Alitalo K, Tammela T, Petrova T V. Lymphangiogenesis in development and human disease.Nature,2005,438(7070):946-953
[149] Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer,2002,2(10):727-739
[150] Bergers G, Benjamin L E. Tumorigenesis and the angiogenic switch. Nat Rev Cancer,2003,3(6):401-410
[151] Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med,2000,6(4):389-395
[152] Hu Y L, Tee M K, Goetzl E J, et al. Lysophosphatidic acid induction of vascular endothelialgrowth factor expression in human ovarian cancer cells. J Natl Cancer Inst,2001,93(10):762-768
[153] Volpert O V, Stellmach V, Bouck N. The modulation of thrombospondin and other naturallyoccurring inhibitors of angiogenesis during tumor progression. Breast Cancer Res Treat,1995,36(2):119-126
[154] O'Reilly M S. Angiostatin: an endogenous inhibitor of angiogenesis and of tumor growth.EXS,1997,79:273-294
[155] O'Reilly M S, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesisand tumor growth. Cell,1997,88(2):277-285
[156] Folkman J, D'Amore P A. Blood vessel formation: what is its molecular basis? Cell,1996,87(7):1153-1155
[157] Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med,1995,1(1):27-31
[158] Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression.Nat Rev Cancer,2002,2(3):161-174
[159] Folkman J, Beckner K. Angiogenesis imaging. Acad Radiol,2000,7(10):783-785
[160] Gerhardt H, Betsholtz C. Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res,2003,314(1):15-23
[161]Howe A K. Regulation of actin-based cell migration by cAMP/PKA. Biochim Biophys Acta,2004,1692(2-3):159-174
[162] Lauffenburger D A. Cell motility. Making connections count. Nature,1996,383(6599):390-391
[163] Lauffenburger D A, Horwitz A F. Cell migration: a physically integrated molecular process.Cell,1996,84(3):359-369
[164] Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res,2007,100(6):782-794
[165] Machesky L M, Hall A. Rho: a connection between membrane receptor signalling and thecytoskeleton. Trends Cell Biol,1996,6(8):304-310
[166] Sepp K J, Auld V J. RhoA and Rac1GTPases mediate the dynamic rearrangement of actinin peripheral glia. Development,2003,130(9):1825-1835
[167] Takai Y, Sasaki T, Tanaka K, et al. Rho as a regulator of the cytoskeleton. Trends BiochemSci,1995,20(6):227-231
[168] Wittmann T, Waterman-Storer C M. Cell motility: can Rho GTPases and microtubules pointthe way? J Cell Sci,2001,114(Pt21):3795-3803
[169] Xu N, Keung B, Myat M M. Rho GTPase controls invagination and cohesive migration ofthe Drosophila salivary gland through Crumbs and Rho-kinase. Dev Biol,2008,321(1):88-100
[170]Luna E J, Hitt A L. Cytoskeleton--plasma membrane interactions. Science,1992,258(5084):955-964
[171] Malliri A, Collard J G. Role of Rho-family proteins in cell adhesion and cancer. Curr OpinCell Biol,2003,15(5):583-589
[172] Sanz-Moreno V, Gadea G, Ahn J, et al. Rac activation and inactivation control plasticity oftumor cell movement. Cell,2008,135(3):510-523
[173] Soga N, Connolly J O, Chellaiah M, et al. Rac regulates vascular endothelial growth factorstimulated motility. Cell Commun Adhes,2001,8(1):1-13
[174] ten Klooster J P, Leeuwen I, Scheres N, et al. Rac1-induced cell migration requiresmembrane recruitment of the nuclear oncogene SET. EMBO J,2007,26(2):336-345
[175] Bompard G, Caron E. Regulation of WASP/WAVE proteins: making a long story short. JCell Biol,2004,166(7):957-962
[176] Noritake J, Watanabe T, Sato K, et al. IQGAP1: a key regulator of adhesion and migration.J Cell Sci,2005,118(Pt10):2085-2092
[177] Lamalice L, Houle F, Jourdan G, et al. Phosphorylation of tyrosine1214on VEGFR2isrequired for VEGF-induced activation of Cdc42upstream of SAPK2/p38. Oncogene,2004,23(2):434-445
[178] Yamazaki D, Suetsugu S, Miki H, et al. WAVE2is required for directed cell migration andcardiovascular development. Nature,2003,424(6947):452-456
[179] Higashida C, Miyoshi T, Fujita A, et al. Actin polymerization-driven molecular movementof mDia1in living cells. Science,2004,303(5666):2007-2010
[180] Kurokawa K, Matsuda M. Localized RhoA activation as a requirement for the induction ofmembrane ruffling. Mol Biol Cell,2005,16(9):4294-4303
[181] van Nieuw Amerongen G P, Koolwijk P, Versteilen A, et al. Involvement of RhoA/Rhokinase signaling in VEGF-induced endothelial cell migration and angiogenesis in vitro.Arterioscler Thromb Vasc Biol,2003,23(2):211-217
[182] Gingras D, Lamy S, Beliveau R. Tyrosine phosphorylation of the vascularendothelial-growth-factor receptor-2(VEGFR-2) is modulated by Rho proteins. Biochem J,2000,348Pt2:273-280
[183] Rousseau S, Houle F, Huot J. Integrating the VEGF signals leading to actin-based motilityin vascular endothelial cells. Trends Cardiovasc Med,2000,10(8):321-327
[184] Qi J H, Claesson-Welsh L. VEGF-induced activation of phosphoinositide3-kinase isdependent on focal adhesion kinase. Exp Cell Res,2001,263(1):173-182
[185] Williams M R, Arthur J S, Balendran A, et al. The role of3-phosphoinositide-dependentprotein kinase1in activating AGC kinases defined in embryonic stem cells. Curr Biol,2000,10(8):439-448
[186] Jaffe A B, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol,2005,21:247-269
[187] Watanabe T, Noritake J, Kaibuchi K. Regulation of microtubules in cell migration. TrendsCell Biol,2005,15(2):76-83
[188] Fukata M, Nakagawa M, Kaibuchi K. Roles of Rho-family GTPases in cell polarisation anddirectional migration. Curr Opin Cell Biol,2003,15(5):590-597
[189] Cook T A, Nagasaki T, Gundersen G G. Rho guanosine triphosphatase mediates theselective stabilization of microtubules induced by lysophosphatidic acid. J Cell Biol,1998,141(1):175-185
[190] Infante A S, Stein M S, Zhai Y, et al. Detyrosinated (Glu) microtubules are stabilized by anATP-sensitive plus-end cap. J Cell Sci,2000,113(Pt22):3907-3919
[191] Palazzo A F, Cook T A, Alberts A S, et al. mDia mediates Rho-regulated formation andorientation of stable microtubules. Nat Cell Biol,2001,3(8):723-729
[192] Daub H, Gevaert K, Vandekerckhove J, et al. Rac/Cdc42and p65PAK regulate themicrotubule-destabilizing protein stathmin through phosphorylation at serine16. J BiolChem,2001,276(3):1677-1680
[193] Wittmann T, Bokoch G M, Waterman-Storer C M. Regulation of microtubule destabilizingactivity of Op18/stathmin downstream of Rac1. J Biol Chem,2004,279(7):6196-6203
[194] Schuyler S C, Pellman D. Microtubule "plus-end-tracking proteins": The end is just thebeginning. Cell,2001,105(4):421-424
[195] Galjart N, Perez F. A plus-end raft to control microtubule dynamics and function. Curr OpinCell Biol,2003,15(1):48-53
[196] Fukata M, Watanabe T, Noritake J, et al. Rac1and Cdc42capture microtubules throughIQGAP1and CLIP-170. Cell,2002,109(7):873-885
[197] Watanabe T, Wang S, Noritake J, et al. Interaction with IQGAP1links APC to Rac1, Cdc42,and actin filaments during cell polarization and migration. Dev Cell,2004,7(6):871-883
[198] Bashour A M, Fullerton A T, Hart M J, et al. IQGAP1, a Rac-and Cdc42-binding protein,directly binds and cross-links microfilaments. J Cell Biol,1997,137(7):1555-1566
[199] Bhatt A, Kaverina I, Otey C, et al. Regulation of focal complex composition anddisassembly by the calcium-dependent protease calpain. J Cell Sci,2002,115(Pt17):3415-3425
[200] Hynes R O. Integrins: bidirectional, allosteric signaling machines. Cell,2002,110(6):673-687
[201] Ananthakrishnan R, Ehrlicher A. The forces behind cell movement. Int J Biol Sci,2007,3(5):303-317
[202] Plastino J, Sykes C. The actin slingshot. Curr Opin Cell Biol,2005,17(1):62-66
[203] Raftopoulou M, Hall A. Cell migration: Rho GTPases lead the way. Dev Biol,2004,265(1):23-32
[204] Faix J, Rottner K. The making of filopodia. Curr Opin Cell Biol,2006,18(1):18-25
[205] Etienne-Manneville S. Actin and microtubules in cell motility: which one is in control?Traffic,2004,5(7):470-477
[206] Boudreau N J, Jones P L. Extracellular matrix and integrin signalling: the shape of things tocome. Biochem J,1999,339(Pt3):481-488
[207] Hamadi A, Bouali M, Dontenwill M, et al. Regulation of focal adhesion dynamics anddisassembly by phosphorylation of FAK at tyrosine397. J Cell Sci,2005,118(Pt19):4415-4425
[208] Subauste M C, Pertz O, Adamson E D, et al. Vinculin modulation of paxillin-FAKinteractions regulates ERK to control survival and motility. J Cell Biol,2004,165(3):371-381
[209] Michael K E, Dumbauld D W, Burns K L, et al. Focal adhesion kinase modulates celladhesion strengthening via integrin activation. Mol Biol Cell,2009,20(9):2508-2519
[210] Norgauer J, Krutmann J, Dobos G J, et al. Actin polymerization, calcium-transients, andphospholipid metabolism in human neutrophils after stimulation with interleukin-8andN-formyl peptide. J Invest Dermatol,1994,102(3):310-314
[211] Romer L H, Birukov K G, Garcia J G. Focal adhesions: paradigm for a signaling nexus. CircRes,2006,98(5):606-616
[212] Li J P, Fu Y N, Chen Y R, et al. JNK pathway-associated phosphatase dephosphorylatesfocal adhesion kinase and suppresses cell migration. J Biol Chem,2010,285(8):5472-5478
[213] Kimura K, Ito M, Amano M, et al. Regulation of myosin phosphatase by Rho andRho-associated kinase (Rho-kinase). Science,1996,273(5272):245-248
[214] Feng J, Ito M, Kureishi Y, et al. Rho-associated kinase of chicken gizzard smooth muscle. JBiol Chem,1999,274(6):3744-3752
[215] Riento K, Ridley A J. Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol CellBiol,2003,4(6):446-456
[216] Ramos E, Wysolmerski R B, Masaracchia R A. Myosin phosphorylation by humancdc42-dependent S6/H4kinase/gammaPAK from placenta and lymphoid cells. ReceptSignal Transduct,1997,7(2):99-110
[217] Chew T L, Masaracchia R A, Goeckeler Z M, et al. Phosphorylation of non-muscle myosinII regulatory light chain by p21-activated kinase (gamma-PAK). J Muscle Res Cell Motil,1998,19(8):839-854
[218] Schultz J, Milpetz F, Bork P, et al. SMART, a simple modular architecture research tool:identification of signaling domains. Proc Natl Acad Sci U S A,1998,95(11):5857-5864
[219] Rebhan M, Chalifa-Caspi V, Prilusky J, et al. GeneCards: a novel functional genomicscompendium with automated data mining and query reformulation support. Bioinformatics,1998,14(8):656-664
[220] Glover J N, Harrison S C. Crystal structure of the heterodimeric bZIP transcription factorc-Fos-c-Jun bound to DNA. Nature,1995,373(6511):257-261
[221] Frank S, Schulthess T, Landwehr R, et al. Characterization of the matrilin coiled-coildomains reveals seven novel isoforms. J Biol Chem,2002,277(21):19071-19079
[222] Mason J M, Arndt K M. Coiled coil domains: stability, specificity, and biologicalimplications. Chembiochem,2004,5(2):170-176
[223] Bouckson-Castaing V, Moudjou M, Ferguson D J, et al. Molecular characterisation ofninein, a new coiled-coil protein of the centrosome. J Cell Sci,1996,109(Pt1):179-190
[224] Wilkinson C J, Carl M, Harris W A. Cep70and Cep131contribute to ciliogenesis inzebrafish embryos. BMC Cell Biol,2009,10:17
[225] Ibanez-Tallon I, Heintz N, Omran H. To beat or not to beat: roles of cilia in developmentand disease. Hum Mol Genet,2003,12Spec No1: R27-35
[226] Bisgrove B W, Yost H J. The roles of cilia in developmental disorders and disease.Development,2006,133(21):4131-4143
[227] Scholey J M. Intraflagellar transport motors in cilia: moving along the cell's antenna. J CellBiol,2008,180(1):23-29
[228] Hubbert C, Guardiola A, Shao R, et al. HDAC6is a microtubule-associated deacetylase.Nature,2002,417(6887):455-458
[229] Shiratsuchi G, Kamiya R, Hirono M. Scaffolding function of the Chlamydomonasprocentriole protein CRC70, a member of the conserved Cep70family. J Cell Sci,2011,124(Pt17):2964-2975
[230] Dippell J, Varlam D E. Early sonographic aspects of kidney morphology in Bardet-Biedlsyndrome. Pediatr Nephrol,1998,12(7):559-563
[231]Dutcher S K. Finding treasures in frozen cells: new centriole intermediates. Bioessays,2007,29(7):630-634
[232] Nakazawa Y, Hiraki M, Kamiya R, et al. SAS-6is a cartwheel protein that establishes the9-fold symmetry of the centriole. Curr Biol,2007,17(24):2169-2174
[233] Matsuura K, Lefebvre P A, Kamiya R, et al. Bld10p, a novel protein essential for basalbody assembly in Chlamydomonas: localization to the cartwheel, the first ninefoldsymmetrical structure appearing during assembly. J Cell Biol,2004,165(5):663-671
[234] Hiraki M, Nakazawa Y, Kamiya R, et al. Bld10p constitutes the cartwheel-spoke tip andstabilizes the9-fold symmetry of the centriole. Curr Biol,2007,17(20):1778-1783
[235] Zhou J, Panda D, Landen J W, et al. Minor alteration of microtubule dynamics causes lossof tension across kinetochore pairs and activates the spindle checkpoint. J Biol Chem,2002,277(19):17200-17208
[236] Delaval B, Doxsey S J. Pericentrin in cellular function and disease. J Cell Biol,2010,188(2):181-190
[237] Kardon J R, Vale R D. Regulators of the cytoplasmic dynein motor. Nat Rev Mol Cell Biol,2009,10(12):854-865
[238] Wade R H. On and around microtubules: an overview. Mol Biotechnol,2009,43(2):177-191
[239] Schiebel E. gamma-tubulin complexes: binding to the centrosome, regulation andmicrotubule nucleation. Curr Opin Cell Biol,2000,12(1):113-118
[240] van der Vaart B, Akhmanova A, Straube A. Regulation of microtubule dynamic instability.Biochem Soc Trans,2009,37(Pt5):1007-1013
[241] Sun X, Shi X, Liu M, et al. Mdp3is a novel microtubule-binding protein that regulatesmicrotubule assembly and stability. Cell Cycle,2011,10(22):3929-3937
[242] Tanenbaum M E, Medema R H. Mechanisms of centrosome separation and bipolar spindleassembly. Dev Cell,2010,19(6):797-806
[243] Siller K H, Doe C Q. Spindle orientation during asymmetric cell division. Nat Cell Biol,2009,11(4):365-374
[244] Pease J C, Tirnauer J S. Mitotic spindle misorientation in cancer--out of alignment and intothe fire. J Cell Sci,2011,124(Pt7):1007-1016
[245] Thompson S L, Bakhoum S F, Compton D A. Mechanisms of chromosomal instability. CurrBiol,2010,20(6): R285-295
[246] Taylor S M, Nevis K R, Park H L, et al. Angiogenic factor signaling regulates centrosomeduplication in endothelial cells of developing blood vessels. Blood,2010,116(16):3108-3117
[247] Shi X, Sun X, Liu M, et al. CEP70protein interacts with gamma-tubulin to localize at thecentrosome and is critical for mitotic spindle assembly. J Biol Chem,2011,286(38):33401-33408
[248] Shi X, Wang J, Yang Y, et al. Cep70promotes microtubule assembly in vitro by increasingmicrotubule elongation. Acta Biochim Biophys Sin (Shanghai),2012,44(5):450-454
[249] Gao J, Sun L, Huo L, et al. CYLD regulates angiogenesis by mediating vascular endothelialcell migration. Blood,2010,115(20):4130-4137
[250] Li D, Xie S, Ren Y, et al. Microtubule-associated deacetylase HDAC6promotesangiogenesis by regulating cell migration in an EB1-dependent manner. Protein Cell,2011,2(2):150-160
[251] Gotlieb A I. The endothelial cytoskeleton: organization in normal and regeneratingendothelium. Toxicol Pathol,1990,18(4Pt1):603-617
[252] Ren X D, Kiosses W B, Schwartz M A. Regulation of the small GTP-binding protein Rhoby cell adhesion and the cytoskeleton. EMBO J,1999,18(3):578-585