中间纤维的功能和研究进展
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摘要
中间纤维(intermediate filaments, IFs)与微丝、微管共同组成细胞骨架的纤维网络体系。除了结构支撑作用,中间纤维在诸多信号转导通路中发挥了重要调控功能。此外,中间纤维还参与调控细胞运动、增殖、分化和凋亡等过程,相关基因突变或翻译后修饰会导致癌症、创伤、炎症、病原体感染及自身免疫等多种疾病。该综述将简要介绍中间纤维参与的细胞功能调控,并重点介绍与其他骨架体系的协同互作及参与相关疾病的调控。中间纤维作为参与多种生物功能和组织特异调控的重要元素,对其深入全面的研究将会对相关生理过程、病理机制和临床治疗具有重要意义。
Intermediate filaments(IFs), together with actin filaments and microtubules comprise a diverse and flexible cytoskeletal system. Besides mechanical support, IFs are involved in a wide range of cell signaling pathways. In addition, IFs-associated functions are essential for cell migration, cell proliferation, cell differentiation and apoptosis. Characteristically, the mutations and posttranslational modifications of IFs were found in various pathological processes, including cancer, tissue regeneration, inflammation, pathogen infection as well as immune responses. This review briefly summarizes the cellular function of IFs, and focuses on its interplay with other cytoskeletal systems and regulation of a variety of diseases. As multifactorial and tissue-specific integrators, the comprehensive study on IFs will contribute to diverse range of pathologies.
Intermediate filaments(IFs), together with actin filaments and microtubules comprise a diverse and flexible cytoskeletal system. Besides mechanical support, IFs are involved in a wide range of cell signaling pathways. In addition, IFs-associated functions are essential for cell migration, cell proliferation, cell differentiation and apoptosis. Characteristically, the mutations and posttranslational modifications of IFs were found in various pathological processes, including cancer, tissue regeneration, inflammation, pathogen infection as well as immune responses. This review briefly summarizes the cellular function of IFs, and focuses on its interplay with other cytoskeletal systems and regulation of a variety of diseases. As multifactorial and tissue-specific integrators, the comprehensive study on IFs will contribute to diverse range of pathologies.
引文
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3 Herrmann H,Strelkov SV,Burkhard P,Aebi U.Intermediate filaments:primary determinants of cell architecture and plasticity.J Clin Invest 2009;119(7):1772-83.
4 Coulombe PA,Wong P.Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds.Nat Cell Biol2004;6(8):699-706.
5 Strelkov SV,Herrmann H,Geisler N,Wedig T,Zimbelmann R,Aebi U,et al.Conserved segments 1A and 2B of the intermediate filament dimer:their atomic structures and role in filament assembly.EMBO J 2014;21(6):1255-66.
6 Block J,Witt H,Candelli A,Danes JC,Peterman EJG,Wuite GJL,et al.Viscoelastic properties of vimentin originate from nonequilibrium conformational changes.Sci Adv 2018;4(6):eaat1161.
7 Leube RE,Schwarz N.Intermediate filaments.Encyclopedia of Cell Biology 2016;2:569-78.
8 Snider NT,Omary MB.Post-translational modifications of intermediate filament proteins:mechanisms and functions.Nat Rev Mol Cell Biol 2014;15(3):163-77.
9 Toivola DM,Strnad P,Habtezion A,Omary MB.Intermediate filaments take the heat as stress proteins.Trends Cell Biol 2010;20(2):79-91.
10 Strnad P,Stumptner C,Zatloukal K,Denk H.Intermediate filament cytoskeleton of the liver in health and disease.Histochem Cell Biol 2008;129(6):735-49.
11 Lai YK,Lee WC,Chen KD.Vimentin serves as a phosphate sink during the apparent activation of protein kinases by okadaic acid in mammalian cells.J Cell Biochem 2010;53(2):161-8
12 Yang L,Tang L,Dai F,Meng G,Yin R,Xu X,et al.Raf-1/CK2and RhoA/ROCK signaling promote TNF-α-mediated endothelial apoptosis via regulating vimentin cytoskeleton.Toxicology 2017;389:74-84.
13 Burikhanov R,Sviripa VM,Hebbar N,Zhang W,Layton WJ,Hamza A,et al.Arylquins target vimentin to trigger Par-4secretion for tumor cell apoptosis.Nat Chem Biol 2014;10(11):924-6.
14 Kim S,Wong P,Coulombe PA.A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growth.Nature2006;441(7091):362-5.
15 Mariani RA,Paranjpe S,Dobrowolski R,Weber GF.14-3-3recruits keratin intermediate filaments to mechanically sensitive cell-cell contacts.bioRxiv 2018.
16 Sahlgren CM,Pallari HM,He T,Chou YH,Goldman RD,Eriksson JE.A nestin scaffold links Cdk5/p35 signaling to oxidant-induced cell death.Embo Journal 2014;25(20):8-19.
17 Huang YL,Wu CM,Shi GY,Wu GC,Lee H,Jiang MJ,et al.Nestin serves as a prosurvival determinant that is linked to the cytoprotective effect of epidermal growth factor in rat vascular smooth muscle cells.J Biochem 2009;146(3):307-15.
18 Oguri T,Inoko A,Shima H,Izawa I,Arimura N,Yamaguchi T,et al.Vimentin-Ser82 as a memory phosphorylation site in astrocytes.Genes Cells 2010;11(5):531-40.
19 Izawa I,Inagaki M.Regulatory mechanisms and functions of intermediate filaments:a study using site-and phosphorylation state-specific antibodies.Cancer Sci 2010;97(3):167-74.
20 Dias E,Matos P,Pereira P,Batoréu MC,Silva MJ,Jordan P.Microcystin-LR activates the ERK1/2 kinases and stimulates the proliferation of the monkey kidney-derived cell line Vero-E6.Toxicol In Vitro 2010;24(6):1689-95.
21 Leduc C,Etiennemanneville S.Intermediate filaments in cell migration and invasion:the unusual suspects.Curr Opin Cell Biol 2015;32:102-12.
22 Tang DD,Gerlach BD.The roles and regulation of the actin cytoskeleton,intermediate filaments and microtubules in smooth muscle cell migration.Resp Res 2017;18(1):54.
23 Tang DD.Intermediate filaments in smooth muscle.Am J Physiol Cell Physiol 2008;294(4):C869.
24 Eckes B,Dogic D,Colucciguyon E,Wang N,Maniotis A,Ingber D,et al.Impaired mechanical stability,migration and contractile capacity in vimentin-deficient fibroblasts.J Cell Sci 1998;111(Pt13):1897-907.
25 Jiang S,Tang DD.Plk1 regulates MEK1/2 and proliferation in airway smooth muscle cells.Resp Res 2015;16(1):1-9.
26 Li J,Wang R,Tang DD.Vimentin dephosphorylation at ser-56 is regulated by type 1 protein phosphatase in smooth muscle.Resp Res 2016;17(1):91.
27 Chung BM,Rotty JD,Coulombe PA.Networking galore:Intermediate filaments and cell migration.Curr Opin Cell Biol2013;25(5):600-12.
28 Kim J,Yang C,Kim EJ,Jang J,Kim SJ,Kang SM,et al.Vimentin filaments regulate integrin-ligand interactions by binding to the cytoplasmic tail of integrinβ3.J Cell Sci 2016;129.
29 Havel LS,Kline ER,Salgueiro AM,Marcus AI.Vimentin regulates lung cancer cell adhesion through a VAV2-Rac1pathway to control focal adhesion kinase activity.Oncogene2015;34(5):1979-90.
30 Burgstaller G,Gregor M,Winter L,Wiche G.Keeping the vimentin network under control:cell-matrix adhesion-associated plectin 1f affects cell shape and polarity of fibroblasts.Mol Biol Cell 2011;21(1):3362-75.
31 Havel LS,Kline ER,Salgueiro AM,Marcus AI.Vimentin regulates lung cancer cell adhesion through a VAV2-Rac1pathway to control focal adhesion kinase activity.Oncogene2015;34(15):1979-90.
32 Gregor M,Osmanagicmyers S,Burgstaller G,Wolfram M,Fischer I,Walko G,et al.Mechanosensing through focal adhesion-anchored intermediate filaments.FASEB J 2014;28(2):715-29.
33 Tang DD.Critical role of actin-associated proteins in smooth muscle contraction,cell proliferation,airway hyperresponsiveness and airway remodeling.Resp Res 2015;16(1):134.
34 Ivaska J,Vuoriluoto K,Huovinen T,Izawa I,Inagaki M,Parker PJ,et al.PKC-mediated phosphorylation of vimentin controls integrin recycling and motility.EMBO J 2005;24(22):3834-45.
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