中科院上海生命科學(xué)院生物化學(xué)與細(xì)胞生物學(xué)研究所,、麻省總醫(yī)院,、哈佛醫(yī)學(xué)院的科學(xué)家在最新一期Developmental Cell上發(fā)表細(xì)胞極性蛋白在上皮細(xì)胞遷移過(guò)程中的調(diào)節(jié)作用機(jī)制有關(guān)進(jìn)展論文。
細(xì)胞移行（cell migration）是一種十分重要的生物學(xué)現(xiàn)象,，比如說(shuō),，在創(chuàng)傷修復(fù)過(guò)程中。aPKC-Par3與PATJ是兩種重要的極性蛋白,，參與調(diào)控上皮細(xì)胞的移行行為,。但是兩種極性蛋白是如何聚集到需移行的細(xì)胞周?chē)模瑓s一直不清楚,。
研究人員鑒別了一種特殊的蛋白,，在外界刺激環(huán)境下具有吸引aPKC-Par3與PATJ蛋白聚集在上皮細(xì)胞周?chē)墓δ堋?/p>
Occludin是一種存在于細(xì)胞連接處的細(xì)胞膜蛋白,。最近的研究發(fā)現(xiàn)，occludin還有鮮為人知的一種新功能,。這種功能體現(xiàn)在創(chuàng)傷愈合過(guò)程中的腎上皮細(xì)胞中,。研究人員發(fā)現(xiàn)，occludin在17小時(shí)內(nèi)能促進(jìn)90%的細(xì)胞完成創(chuàng)口愈合過(guò)程,。而對(duì)occludin進(jìn)行功能性缺失研究發(fā)現(xiàn),，只有28.6%的細(xì)胞能完成創(chuàng)口愈合過(guò)程。Occludin被發(fā)現(xiàn)存在于細(xì)胞連接處,，促進(jìn)細(xì)胞移行,。
研究人員同時(shí)發(fā)現(xiàn)，aPKC-Par3與PATJ也聚集在移行細(xì)胞周?chē)?，但是在occludin功能缺失的細(xì)胞周?chē)淮嬖赼PKC-Par3/PATJ復(fù)合物,。細(xì)胞移行缺陷的組織失去正常的愈合能力。這些研究數(shù)據(jù)表明,，occludin具有吸引aPKC-Par3/PATJ復(fù)合物到移行細(xì)胞周?chē)墓δ?。研究發(fā)現(xiàn)occludin具有激活PI3K的功能，PI3K是一種在細(xì)胞移行過(guò)程中重要的功能酶,。
Occludin具有促進(jìn)aPKC-Par3/PATJ復(fù)合物和PI3K的功能,，是維持細(xì)胞移行的重要蛋白。（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 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.
