肠黏膜上皮组织紧密连接的生物学功能和作用机理
|
摘要
紧密连接(TJ)是肠黏膜上皮细胞间的主要连接方式,对维持黏膜上皮细胞极性及调节肠屏障的通透性发挥着重要的作用。TJ在黏膜上皮细胞间形成限制溶质和物质运动的细胞屏障。总的来说,TJ的结构可以概括为跨膜屏障蛋白与周围的脚手架蛋白组成的间隔。在这个复杂的网络中有许多相关的信号蛋白,影响屏障和更广泛的细胞功能。本文从TJ在肠黏膜上皮中的生物学功能、分子调控机制及当前研究现状等作综合阐述。
Tight junction is the main connection between intestinal epithelial cells,which plays an important role in maintenance of epithelial cell polarity and regulation of the permeability of the intestinal barrier.Tight junction creates an intercellular barrier limiting paracellular movement of solutes and materials across epithelia.In general,the architecture can be conceptualized into compartments with the transmembrane barrier proteins linked to peripheral scaffolding proteins.Within the complex network,tight junction is associated with many signaling proteins that affect the barrier and broader cell functions.This review was about biological function,molecular mechanisms and current research status of tight junction in intestinal mucosal epithelium.
Tight junction is the main connection between intestinal epithelial cells,which plays an important role in maintenance of epithelial cell polarity and regulation of the permeability of the intestinal barrier.Tight junction creates an intercellular barrier limiting paracellular movement of solutes and materials across epithelia.In general,the architecture can be conceptualized into compartments with the transmembrane barrier proteins linked to peripheral scaffolding proteins.Within the complex network,tight junction is associated with many signaling proteins that affect the barrier and broader cell functions.This review was about biological function,molecular mechanisms and current research status of tight junction in intestinal mucosal epithelium.
引文
[1]FURUSE M,FUJITA K,HIIRAIG T,et al.Claudin-1and claudin-2:novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin[J].The Journal of Cell Biology,2001,141(7):1539-1550.
[2]MATSUDA M,KUBO A,FURUSE M,et al.A peculiar internalization of claudins,tight junction-specific adhesion molecules,during the intercellular movement of epithelial cells[J].The Journal of Cell Biology,2004,117:1247-1257.
[3]YEAMAN C,GRINDSTAFF K K,NELSON W J.New perspectives on mechanisms involved in generating epithelial cell Polarity[J].Physiology Review,2005,79(1):73-98.
[4]CITI S,DENISENKO N.Phosphorylation of the tight junction protein cingulin and the effects of protein kinase inhibitors and activators in MDCK epithelial cells[J].Journal of Cell Science,2005,108:2917-2926.
[5]TSUKITA S,FURUSE M.Occludin and claudins in tight-junction strands:leading or supporting Players?[J].Trends in Cell Biology,1999,9(7):268-273.
[6]STEVENSON B R,SILICIANO J D,MOOSEKER M S,et al.Identification of ZO-1:a high molecular weight polypeptide associated with the tight junction(zonula occludens)in a variety of epithelia[J].The Journal of Cell Biology,2005,103(3):755-766.
[7]GUMBINER B,LOWENKOPF T,APATIRA D.Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1[J].Proceedings of the National Academy of Sciences of the United States of America,2005,88(8):3460-3464.
[8]HASKINS J,GU L J,WITTCHEN E S,et al.ZO-3,a novel member of the MAGUK protein family found at the tight junction interacts with ZO-1and occludin[J].The Journal of Cell Biology,2005,141:199-208.
[9]GONZLEZ-MARISCAL L,BETANZOS A,VILA-FLORES A.MAGUK proteins:structure and role in the tight junction[J].Seminars in Cell&Developmental Biology,2000,11(4):315-324.
[10]BAUER H,ZWEIMUELLER-MAYER J,STEINBACHER P,et al.The dual role of zonula occludens(ZO)proteins[J].Journal of Biomedicine and Biotechnology,2010,2010:402593.
[11]LOPEZ-BAYGHEN E,JARAMILLOY BE,HUERTA M,et al.TJ proteins that make round trips to the nucleus[M]//GONZALEZ-MARISCAL L.Tight junctions.[S.l.]:Springer,2006:76-100.
[12]WILLIAMS A F,BARCLAY A N.The immunoglobulin superfamily-domains for cell surface recognition[J].Annual Review of Immunology,2005,6(1):381-405.
[13]MALERGUE F,GALLAND F,MARTIN F,et al.A novel immunoglobulin superfamily junctional molecule expressed by antigen presenting cells,endothelial cells and platelets[J].Molecular Immunology,2005,35(17):1111-1119.
[14]MARTN-PADURA I,LOSTAGLIO S,SCHNEEMANN M,et al.Junctional adhesion molecule,a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration[J].The Journal of Cell Biology,2005,142(1):117-127.
[15]CUNNINGHAM S A,ARRATE M P,RODRIGUEZ J M,et al.A novel protein with homology to the junctional adhesion molecule.Characterization of leukocyte interactions[J].The Journal of Biology Chemistry,2000,275:34750-34756.
[16]PALMERI D,VAN ZANTE A,HUANG C C,et al.Vascular endothelial junction-associated molecule,a novel member of the immunoglobulin superfamily,is localized to intercellular boundaries of endothelial cells[J].The Journal of Biology Chemistry,2000,275(25):19139-19145.
[17]ARRATE M P,RODRIGUEZ J M,TRAN T M,et al.Cloning of human junctional adhesion molecule 3(JAM3)and its identification as the JAM2counterreceptor[J].The Journal of Biology Chemistry,2001,276(49):45826-45832.
[18]AURRAND-LIONS M,DUNCAN L,BALLESTREM C,et al.JAM-2,a novel immunoglobulin superfamily molecule,expressed by endothelial and lymphatic cells[J].The Journal of Biology Chemistry,2001,276(4):2733-2741.
[19]HIRABAYASHI S,TAJIMA M,YAO I,et al.JAM-4,ajunctional cell adhesion molecule interacting with a tight junction protein,MAGI-1[J].Molecular and Cellular Biology,2003,23:4267-4282.
[20]MADARA J L.Intestinal absorptive cell tight junctions are linked to cytoskeleton[J].American Journal of Physiology:Cell Physiology,2005,253(1):C171-C175.
[21]WATSON C J,ROWLAND M,WARHURST G.Functional modeling of tight junctions in intestinal cell monolayers using polyethylene glycol oligomers[J].American Journal of Physiology:Cell Physiology,2001,281(2):388-397.
[22]TANG V W,GOODENOUGH D A.Paracellular ion channel at the tight junction[J].Biophysical Journal,2003,84(3):1660-1673.
[23]YU A S L,ENCK A H,LENCER W I,et al.Claudin-8expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation[J].The Journal of Biology Chemistry,2003,278(19):17350-17359.
[24]ENCK A H,BERGER U V,YU A S L.Claudin-2is selectively expressed in proximal nephron in mouse kidney[J].American Journal of Physiology:Renal Physiology,2001,281(5):F966-F974.
[25]KIUCHI-SAISHIN Y,GOTOH S,FURUSE M,et al.Differential expression patterns of claudins,tight junction membrane proteins in mouse nephron segments[J].Journal of the American Society of Nephrology,2002,13(4):875-886.
[26]COLEGIO O R,VAN ITALLIE C M,RAHNER C,et al.Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture[J].American Journal of Physiology:Cell Physiology,2003,284(6):C1346-C1354.
[27]FURUSE M,FURUSE K,SASAKI H,et al.Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2into Madin-Darby canine kidneyⅠcells[J].The Journal of Biology,2001,153(2):263-272.
[28]HOLLANDER D,VADHEIM C M,BRETTHOLZ E,et al.Increased intestinal permeability in patients with Crohn’s disease and their relatives.A possible etiologic factor[J].Annals of Internal Medicine,2005,105(6):883-885.
[29]YAMAGUCHI Y,DALLE-MOLLE E,HARDISON W G.VasoPressin and A23187stimulate phosphorylaiton of myosin light chain-1in isolated rat hepatocytes[J].American Journal of Physiology:Gastrointestinal and Liver Physiology,2005,261(2):G312-G319.
[30]BEHLENS J,VAKAET L,FRIIS R,et al.Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRCgene[J].The Journal of Biology,2005,120(3):757-766.
[31]MEYER T N,HUNT J,SCHWESINGER C,et al.Gα12 regulates epithelial cell junctions through Src tyrosine kinases[J].American Journal of Physiology:Cell Physiology,2003,285(5):C1281-C1293.
[32]GOPALAKRISHNAN S,RAMAN N,ATKINSON S J,et al.Rho GTPase signaling regulates tight junction assembly and Protects tight junctions during ATP depletion[J].American Journal of Physiology:Cell Physiology,2005,275(3):C798-C809.
[33]CLAASSEN N,COETZER H,STEINMANN C M L,et al.The effect of different n-6n-3essential fatty acid ratios on calcium balance and bone in rats[J].Prostaglandins,Leukotrienes and Essential Fatty Acids,1995,53(1):13-19.
[34]FUJITA K,KATAHIRA J,HORIGUCHI Y,et al.Clostridium perfringens enterotoxin binds to the second extracellular loop of claudin-3,a tight junction integral membrane protein[J].FEBS Letters,2000,476(3):258-261.
[35]ODENBREIT S,PLS J,SEDLMAIER B,et al.Translocation of Helicobacter pylori CagA into gastric epithelial cells by typeⅣsecretion[J].Science,2000,287(5457):1497-1500.
[36]AMIEVA M R,VOGELMANN R,COVACCI A,et al.Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA[J].Science,2005,300(5624):1430-1434.
[2]MATSUDA M,KUBO A,FURUSE M,et al.A peculiar internalization of claudins,tight junction-specific adhesion molecules,during the intercellular movement of epithelial cells[J].The Journal of Cell Biology,2004,117:1247-1257.
[3]YEAMAN C,GRINDSTAFF K K,NELSON W J.New perspectives on mechanisms involved in generating epithelial cell Polarity[J].Physiology Review,2005,79(1):73-98.
[4]CITI S,DENISENKO N.Phosphorylation of the tight junction protein cingulin and the effects of protein kinase inhibitors and activators in MDCK epithelial cells[J].Journal of Cell Science,2005,108:2917-2926.
[5]TSUKITA S,FURUSE M.Occludin and claudins in tight-junction strands:leading or supporting Players?[J].Trends in Cell Biology,1999,9(7):268-273.
[6]STEVENSON B R,SILICIANO J D,MOOSEKER M S,et al.Identification of ZO-1:a high molecular weight polypeptide associated with the tight junction(zonula occludens)in a variety of epithelia[J].The Journal of Cell Biology,2005,103(3):755-766.
[7]GUMBINER B,LOWENKOPF T,APATIRA D.Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1[J].Proceedings of the National Academy of Sciences of the United States of America,2005,88(8):3460-3464.
[8]HASKINS J,GU L J,WITTCHEN E S,et al.ZO-3,a novel member of the MAGUK protein family found at the tight junction interacts with ZO-1and occludin[J].The Journal of Cell Biology,2005,141:199-208.
[9]GONZLEZ-MARISCAL L,BETANZOS A,VILA-FLORES A.MAGUK proteins:structure and role in the tight junction[J].Seminars in Cell&Developmental Biology,2000,11(4):315-324.
[10]BAUER H,ZWEIMUELLER-MAYER J,STEINBACHER P,et al.The dual role of zonula occludens(ZO)proteins[J].Journal of Biomedicine and Biotechnology,2010,2010:402593.
[11]LOPEZ-BAYGHEN E,JARAMILLOY BE,HUERTA M,et al.TJ proteins that make round trips to the nucleus[M]//GONZALEZ-MARISCAL L.Tight junctions.[S.l.]:Springer,2006:76-100.
[12]WILLIAMS A F,BARCLAY A N.The immunoglobulin superfamily-domains for cell surface recognition[J].Annual Review of Immunology,2005,6(1):381-405.
[13]MALERGUE F,GALLAND F,MARTIN F,et al.A novel immunoglobulin superfamily junctional molecule expressed by antigen presenting cells,endothelial cells and platelets[J].Molecular Immunology,2005,35(17):1111-1119.
[14]MARTN-PADURA I,LOSTAGLIO S,SCHNEEMANN M,et al.Junctional adhesion molecule,a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration[J].The Journal of Cell Biology,2005,142(1):117-127.
[15]CUNNINGHAM S A,ARRATE M P,RODRIGUEZ J M,et al.A novel protein with homology to the junctional adhesion molecule.Characterization of leukocyte interactions[J].The Journal of Biology Chemistry,2000,275:34750-34756.
[16]PALMERI D,VAN ZANTE A,HUANG C C,et al.Vascular endothelial junction-associated molecule,a novel member of the immunoglobulin superfamily,is localized to intercellular boundaries of endothelial cells[J].The Journal of Biology Chemistry,2000,275(25):19139-19145.
[17]ARRATE M P,RODRIGUEZ J M,TRAN T M,et al.Cloning of human junctional adhesion molecule 3(JAM3)and its identification as the JAM2counterreceptor[J].The Journal of Biology Chemistry,2001,276(49):45826-45832.
[18]AURRAND-LIONS M,DUNCAN L,BALLESTREM C,et al.JAM-2,a novel immunoglobulin superfamily molecule,expressed by endothelial and lymphatic cells[J].The Journal of Biology Chemistry,2001,276(4):2733-2741.
[19]HIRABAYASHI S,TAJIMA M,YAO I,et al.JAM-4,ajunctional cell adhesion molecule interacting with a tight junction protein,MAGI-1[J].Molecular and Cellular Biology,2003,23:4267-4282.
[20]MADARA J L.Intestinal absorptive cell tight junctions are linked to cytoskeleton[J].American Journal of Physiology:Cell Physiology,2005,253(1):C171-C175.
[21]WATSON C J,ROWLAND M,WARHURST G.Functional modeling of tight junctions in intestinal cell monolayers using polyethylene glycol oligomers[J].American Journal of Physiology:Cell Physiology,2001,281(2):388-397.
[22]TANG V W,GOODENOUGH D A.Paracellular ion channel at the tight junction[J].Biophysical Journal,2003,84(3):1660-1673.
[23]YU A S L,ENCK A H,LENCER W I,et al.Claudin-8expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation[J].The Journal of Biology Chemistry,2003,278(19):17350-17359.
[24]ENCK A H,BERGER U V,YU A S L.Claudin-2is selectively expressed in proximal nephron in mouse kidney[J].American Journal of Physiology:Renal Physiology,2001,281(5):F966-F974.
[25]KIUCHI-SAISHIN Y,GOTOH S,FURUSE M,et al.Differential expression patterns of claudins,tight junction membrane proteins in mouse nephron segments[J].Journal of the American Society of Nephrology,2002,13(4):875-886.
[26]COLEGIO O R,VAN ITALLIE C M,RAHNER C,et al.Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture[J].American Journal of Physiology:Cell Physiology,2003,284(6):C1346-C1354.
[27]FURUSE M,FURUSE K,SASAKI H,et al.Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2into Madin-Darby canine kidneyⅠcells[J].The Journal of Biology,2001,153(2):263-272.
[28]HOLLANDER D,VADHEIM C M,BRETTHOLZ E,et al.Increased intestinal permeability in patients with Crohn’s disease and their relatives.A possible etiologic factor[J].Annals of Internal Medicine,2005,105(6):883-885.
[29]YAMAGUCHI Y,DALLE-MOLLE E,HARDISON W G.VasoPressin and A23187stimulate phosphorylaiton of myosin light chain-1in isolated rat hepatocytes[J].American Journal of Physiology:Gastrointestinal and Liver Physiology,2005,261(2):G312-G319.
[30]BEHLENS J,VAKAET L,FRIIS R,et al.Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRCgene[J].The Journal of Biology,2005,120(3):757-766.
[31]MEYER T N,HUNT J,SCHWESINGER C,et al.Gα12 regulates epithelial cell junctions through Src tyrosine kinases[J].American Journal of Physiology:Cell Physiology,2003,285(5):C1281-C1293.
[32]GOPALAKRISHNAN S,RAMAN N,ATKINSON S J,et al.Rho GTPase signaling regulates tight junction assembly and Protects tight junctions during ATP depletion[J].American Journal of Physiology:Cell Physiology,2005,275(3):C798-C809.
[33]CLAASSEN N,COETZER H,STEINMANN C M L,et al.The effect of different n-6n-3essential fatty acid ratios on calcium balance and bone in rats[J].Prostaglandins,Leukotrienes and Essential Fatty Acids,1995,53(1):13-19.
[34]FUJITA K,KATAHIRA J,HORIGUCHI Y,et al.Clostridium perfringens enterotoxin binds to the second extracellular loop of claudin-3,a tight junction integral membrane protein[J].FEBS Letters,2000,476(3):258-261.
[35]ODENBREIT S,PLS J,SEDLMAIER B,et al.Translocation of Helicobacter pylori CagA into gastric epithelial cells by typeⅣsecretion[J].Science,2000,287(5457):1497-1500.
[36]AMIEVA M R,VOGELMANN R,COVACCI A,et al.Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA[J].Science,2005,300(5624):1430-1434.