近日，國際學(xué)術(shù)期刊Developmental Cell發(fā)表了生化與細(xì)胞所陳正軍研究組有關(guān)細(xì)胞極性蛋白參與細(xì)胞遷移過程的最新研究成果,。這項研究發(fā)現(xiàn),，重要的細(xì)胞緊密聯(lián)接蛋白,，又稱封閉蛋白（Occludin），在上皮細(xì)胞的定向遷移過程中定位于遷移的上皮細(xì)胞的遷移前緣,，可能參與細(xì)胞定向遷移的極性的形成和穩(wěn)定,，由此調(diào)控細(xì)胞定向遷移活動。
細(xì)胞遷移是一種非常重要的細(xì)胞活動現(xiàn)象,，它在生物體發(fā)育過程以及機(jī)體穩(wěn)態(tài)維持方面起著非常重要的作用,，也和許多疾病的發(fā)生發(fā)展緊密相關(guān)。細(xì)胞遷移過程及其分子調(diào)控網(wǎng)絡(luò)非常復(fù)雜,，迄今為止,，遷移細(xì)胞的極性如何形成，極性蛋白如何被招募到上皮細(xì)胞遷移前緣等機(jī)制,，以及極性蛋白的下游信號傳導(dǎo)通路仍很不清楚,。
陳正軍研究組杜丹博士通過細(xì)胞生物學(xué)和原子粒顯微鏡等一系列技術(shù)和方法發(fā)現(xiàn)了四次跨膜封閉蛋白Occludin定位并富集于遷移的上皮細(xì)胞前緣，Occludin表達(dá)被干擾后,，明顯影響其在細(xì)胞遷移前緣的定位,，并造成細(xì)胞微管組織結(jié)構(gòu)紊亂，同時微管組織中心（MTOC）重定向也明顯異常,；分子機(jī)制的研究結(jié)果證明Occludin能與aPKC和PI3K結(jié)合,，且激活aPKC和PI3K信號通路，借此，可能參與調(diào)控了微管組織中心定位,、細(xì)胞骨架組織和細(xì)胞偽足突觸伸展等過程,。這些研究發(fā)現(xiàn)提高了人們對遷移細(xì)胞極性的形成和穩(wěn)定，以及細(xì)胞生命活動—細(xì)胞極性和細(xì)胞遷移—內(nèi)在生物學(xué)相關(guān)性的認(rèn)識,，同時也為了解胚胎發(fā)育過程和愈傷過程增添了新的內(nèi)容,。（生物谷Bioon.com）
生物谷推薦原始出處：
Developmental Cell, Volume 18, Issue 1, 52-63, 19 January 2010 DOI:10.1016/j.devcel.2009.12.008
The Tight Junction Protein, Occludin, Regulates the Directional Migration of Epithelial Cells
Dan Du, Feilai Xu, Lihou Yu, Chenyi Zhang, Xuefeng Lu, Haixin Yuan, Qin Huang, Fan Zhang, Hongyan Bao, Lianghui Jia, Xunwei Wu, Xueliang Zhu, Xiaohui Zhang, Zhe Zhang, Zhengjun Chen
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA Corresponding author
Cell polarity proteins regulate tight junction formation and directional migration in epithelial cells. To date, the mechanism by which these polarity proteins assemble at the leading edge of migrating epithelial cells remains unclear. We report that occludin, a transmembrane protein, is localized at the leading edge of migrating cells and regulates directional cell migration. During migration, occludin knockdown disrupted accumulation of aPKC-Par3 and PATJ at the leading edge, and led to a disorganized microtubule network and defective reorientation of the microtubule organization center (MTOC). Phosphorylation of occludin at tyrosine 473 residue allowed recruitment of p85α to the leading edge via association with its C-terminal SH2 domain. Loss of occludin attenuated activation of PI3K, leading to disorganization of the actin cytoskeleton and reduced cell protrusions. Our data indicate that occludin is required for the leading-edge localization of polarity proteins aPKC-Par3 and PATJ and promotes cell protrusion by regulating membrane-localized activation of PI3K.
