Neogenin调控成骨分化机制的研究进展
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摘要
再生蛋白neogenin属于结直肠癌缺失蛋白(DCC)家族成员,通过结合不同的配体如神经导向因子netrin和排斥性导向分子(RGM)参与机体内稳态的维持、组织生成、血管发生、铁代谢调节、免疫调控、细胞分化、增殖、迁移及凋亡等诸多生理病理过程。有关neogenin调控成骨分化的研究尚处于早期阶段,其调控机制还不明确。为了更好地探究neogenin的功能特性,该文就有关neogenin的分子特征和分布、生理功能及其经BMP信号通路调控成骨分化方面的研究进展进行综述。
Neogenin is a member of the DC C( deleted in colorectal cancer) family which involves in many physiological and pathological processes such as body homeostasis, tissue formation, angiogenesis, iron metabolism, immunoregulation, cell differentiation, proliferation, migration, and apoptosis through interacting with different ligands such as neuronal guidance cues( netrin) and repulsive guidance molecule( RGM).However, research on the osteogenesis modulated by neogenin is still in its infancy. This paper reviews the research progresses of neogenin, which involve its molecular characteristics, distribution, physiological functions,and roles in modulating osteogenesis through BM P signaling pathway.
Neogenin is a member of the DC C( deleted in colorectal cancer) family which involves in many physiological and pathological processes such as body homeostasis, tissue formation, angiogenesis, iron metabolism, immunoregulation, cell differentiation, proliferation, migration, and apoptosis through interacting with different ligands such as neuronal guidance cues( netrin) and repulsive guidance molecule( RGM).However, research on the osteogenesis modulated by neogenin is still in its infancy. This paper reviews the research progresses of neogenin, which involve its molecular characteristics, distribution, physiological functions,and roles in modulating osteogenesis through BM P signaling pathway.
引文
[1]Zhou Z,Xie J,Lee D,et al.Neogenin regulation of BMP-induced canonical Smad signaling and endochondral bone formation[J].Dev Cell,2010,19(1):90-102.
[2]Hagihara M,Endo M,Hata K,et al.Neogenin,a receptor for bone morphogenetic proteins[J].J Biol Chem,2011,286(7):5157-5165.
[3]Tian C,Liu J.Repulsive guidance molecules(RGMs)and neogenin in bone morphogenetic protein(BMP)signaling[J].Mol Reprod Dev,2013,80(9):700-717.
[4]Itokazu T,Fujita Y,Takahashi R,et al.Identification of the neogeninbinding site on the repulsive guidance molecule[J].PLoS One,2012,7(3):e32791.
[5]Severyn CJ,Shinde U,Rotwein P.Molecular biology,genetics and biochemistry of the repulsive guidance molecule family[J].Biochem J,2009,422(3):393-403.
[6]吴新民.Neogenin在神经胶质瘤发展中的作用及其机制的研究[D].吉林:吉林大学,2012.
[7]Rodriguez A,Pan P,Parkkila S.Expression studies of neogenin and its ligand hemojuvelin in mouse tissues[J].J Histochem Cytochem,2007,55(1):85-96.
[8]Conrad S,Stimpfle F,Montazeri S,et al.RGMb controls aggregation and migration of neogenin-positive cells in vitro and in vivo[J].Mol Cell Neurosci,2010,43(2):222-231.
[9]Liu Y,Peng Y,Dai PG,et al.Differential regulation of myosin X movements by its cargos,DCC and neogenin[J].J Cell Sci,2012,125(Pt 3):751-762.
[10]Bae GU,Yang YJ,Jiang G,et al.Neogenin regulates skeletal myofiber size and focal adhesion kinase and extracellular signalregulated kinase activities in vivo and in vitro[J].Mol Biol Cell,2009,20(23):4920-4931.
[11]钟少平.Neogenin/netrin-1对早孕滋养细胞生物行为及胎盘循环障碍的影响[D].湖北:华中科技大学,2010.
[12]Hinck L,Silberstein GB.Key stages in mammary gland development:the mammary end bud as a motile organ[J].Breast Cancer Res.2005,7(6):245-251.
[13]孟晨玲,魏全伟,茆达干.RGMb/DRAGON BMP信号转导[J].中国生物化学与分子生物学报,2013,29(6):497-505.
[14]Zhang AS,West AP Jr,Wyman AE,et al.Interaction of hemojuvelinwith neogenin results in iron accumulation in human embryonic kidney293 cells[J].J Biol Chem,2005,280(40):33885-33894.
[15]Corradini E,Babitt JL,Lin HY.The RGM/DRAGON family of BMP coreceptors[J].Cytokine Growth Factor Rev,2009,20(5-6):389-398.
[16]Lee DH,Zhou LJ,Zhou Z,et al.Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis[J].Blood,2010,115(15):3136-45.
[17]Konig K,Gatidou D,Granja T,et al.The axonal guidance receptor neogenin promotes acute inflammation[J].PLoS ONE,2012,7(3):e32145.
[18]那键,孙大辉,谷贵山,等.骨形态发生蛋白的细胞内信息传导机制[J].中国老年学杂志,2008,28(24):2511-2513.
[19]Bragdon B,Moseychuk O,Saldanha S,et al.Bone morphogenetic proteins:a critical review[J].Cell Signal,2011,23(4):609-620.
[20]Massague J.TGF-beta signalling in context[J].Nat Rev Mol Cell Biol,2012,13(10):616-630.
[21]Xu P,Liu J,Derynck R.Post-translational regulation of TGF-beta receptor and Smad signaling[J].FEBS Lett,2012,586(14):1871-1884.
[22]Heldin CH,Moustakas A.Role of Smads in TGFβsignaling[J].Cell Tissue Res,2012,347(1):21-36.
[23]Huang F,Chen YG.Regulation of TGF-βreceptor activity[J].Cell Biosci,2012,2:9-18.
[24]Ramel MC,Hill CS.Spatial regulation of BMP activity[J].FEBS Lett,2012,586(14):1929-1941.
[25]Cai J,Pardali E,Sanchez-Duffhues G,et al.BMP signaling in vascular diseases[J].FEBS Lett,2012,586(14):1993-2002.
[26]Zakin L,De Robertis EM.Extracellular regulation of BMP signaling[J].Curr Biol,2010,20(3):R89-R92.
[27]Bilandzic M,Stenvers KL.Betaglycan:a multifunctional accessory[J].Mol Cell Endocrinol,2011,339(1-2):180-189.
[28]Taneja-Bageshwar S,Gumienny TL.Two functional domains in C.elegans glypican LON-2 can independently inhibit BMP-like signaling[J].Dev Biol,2012,371(1):66-76.
[29]Kanomata K,Kokabu S,Nojima J,et al.DRAGON,a GPIanchored membrane protein,inhibits BMP signaling in C2C12myoblasts[J].Genes Cells,2009,14(6):695-702.
[30]Babitt JL,Zhang Y,Samad TA,et al.Repulsive guidance molecule(RGMa),a DRAGON homologue,is a bone morphogenetic protein coreceptor[J].J Biol Chem,2005,280(33):29820-29827.
[31]Xia Y,Yu PB,Sidis Y,et al.Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein(BMP)typeⅡreceptors by BMP2 and BMP4[J].J Biol Chem,2007,282(25):18129-18140.
[32]梁吉华,孙玉强.异位骨化发病机制的研究进展[J].中国组织工程研究与临床康复,2008,12(50):9941-9945.
[2]Hagihara M,Endo M,Hata K,et al.Neogenin,a receptor for bone morphogenetic proteins[J].J Biol Chem,2011,286(7):5157-5165.
[3]Tian C,Liu J.Repulsive guidance molecules(RGMs)and neogenin in bone morphogenetic protein(BMP)signaling[J].Mol Reprod Dev,2013,80(9):700-717.
[4]Itokazu T,Fujita Y,Takahashi R,et al.Identification of the neogeninbinding site on the repulsive guidance molecule[J].PLoS One,2012,7(3):e32791.
[5]Severyn CJ,Shinde U,Rotwein P.Molecular biology,genetics and biochemistry of the repulsive guidance molecule family[J].Biochem J,2009,422(3):393-403.
[6]吴新民.Neogenin在神经胶质瘤发展中的作用及其机制的研究[D].吉林:吉林大学,2012.
[7]Rodriguez A,Pan P,Parkkila S.Expression studies of neogenin and its ligand hemojuvelin in mouse tissues[J].J Histochem Cytochem,2007,55(1):85-96.
[8]Conrad S,Stimpfle F,Montazeri S,et al.RGMb controls aggregation and migration of neogenin-positive cells in vitro and in vivo[J].Mol Cell Neurosci,2010,43(2):222-231.
[9]Liu Y,Peng Y,Dai PG,et al.Differential regulation of myosin X movements by its cargos,DCC and neogenin[J].J Cell Sci,2012,125(Pt 3):751-762.
[10]Bae GU,Yang YJ,Jiang G,et al.Neogenin regulates skeletal myofiber size and focal adhesion kinase and extracellular signalregulated kinase activities in vivo and in vitro[J].Mol Biol Cell,2009,20(23):4920-4931.
[11]钟少平.Neogenin/netrin-1对早孕滋养细胞生物行为及胎盘循环障碍的影响[D].湖北:华中科技大学,2010.
[12]Hinck L,Silberstein GB.Key stages in mammary gland development:the mammary end bud as a motile organ[J].Breast Cancer Res.2005,7(6):245-251.
[13]孟晨玲,魏全伟,茆达干.RGMb/DRAGON BMP信号转导[J].中国生物化学与分子生物学报,2013,29(6):497-505.
[14]Zhang AS,West AP Jr,Wyman AE,et al.Interaction of hemojuvelinwith neogenin results in iron accumulation in human embryonic kidney293 cells[J].J Biol Chem,2005,280(40):33885-33894.
[15]Corradini E,Babitt JL,Lin HY.The RGM/DRAGON family of BMP coreceptors[J].Cytokine Growth Factor Rev,2009,20(5-6):389-398.
[16]Lee DH,Zhou LJ,Zhou Z,et al.Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis[J].Blood,2010,115(15):3136-45.
[17]Konig K,Gatidou D,Granja T,et al.The axonal guidance receptor neogenin promotes acute inflammation[J].PLoS ONE,2012,7(3):e32145.
[18]那键,孙大辉,谷贵山,等.骨形态发生蛋白的细胞内信息传导机制[J].中国老年学杂志,2008,28(24):2511-2513.
[19]Bragdon B,Moseychuk O,Saldanha S,et al.Bone morphogenetic proteins:a critical review[J].Cell Signal,2011,23(4):609-620.
[20]Massague J.TGF-beta signalling in context[J].Nat Rev Mol Cell Biol,2012,13(10):616-630.
[21]Xu P,Liu J,Derynck R.Post-translational regulation of TGF-beta receptor and Smad signaling[J].FEBS Lett,2012,586(14):1871-1884.
[22]Heldin CH,Moustakas A.Role of Smads in TGFβsignaling[J].Cell Tissue Res,2012,347(1):21-36.
[23]Huang F,Chen YG.Regulation of TGF-βreceptor activity[J].Cell Biosci,2012,2:9-18.
[24]Ramel MC,Hill CS.Spatial regulation of BMP activity[J].FEBS Lett,2012,586(14):1929-1941.
[25]Cai J,Pardali E,Sanchez-Duffhues G,et al.BMP signaling in vascular diseases[J].FEBS Lett,2012,586(14):1993-2002.
[26]Zakin L,De Robertis EM.Extracellular regulation of BMP signaling[J].Curr Biol,2010,20(3):R89-R92.
[27]Bilandzic M,Stenvers KL.Betaglycan:a multifunctional accessory[J].Mol Cell Endocrinol,2011,339(1-2):180-189.
[28]Taneja-Bageshwar S,Gumienny TL.Two functional domains in C.elegans glypican LON-2 can independently inhibit BMP-like signaling[J].Dev Biol,2012,371(1):66-76.
[29]Kanomata K,Kokabu S,Nojima J,et al.DRAGON,a GPIanchored membrane protein,inhibits BMP signaling in C2C12myoblasts[J].Genes Cells,2009,14(6):695-702.
[30]Babitt JL,Zhang Y,Samad TA,et al.Repulsive guidance molecule(RGMa),a DRAGON homologue,is a bone morphogenetic protein coreceptor[J].J Biol Chem,2005,280(33):29820-29827.
[31]Xia Y,Yu PB,Sidis Y,et al.Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein(BMP)typeⅡreceptors by BMP2 and BMP4[J].J Biol Chem,2007,282(25):18129-18140.
[32]梁吉华,孙玉强.异位骨化发病机制的研究进展[J].中国组织工程研究与临床康复,2008,12(50):9941-9945.