中科院上海生命科学院生物化学与细胞生物学研究所、麻省总医院、哈佛医学院的科学家在最新一期Developmental Cell上发表细胞极性蛋白在上皮细胞迁移过程中的调节作用机制有关进展论文。
细胞移行（cell migration）是一种十分重要的生物学现象，比如说，在创伤修复过程中。aPKC-Par3与PATJ是两种重要的极性蛋白，参与调控上皮细胞的移行行为。但是两种极性蛋白是如何聚集到需移行的细胞周围的，却一直不清楚。
研究人员鉴别了一种特殊的蛋白，在外界刺激环境下具有吸引aPKC-Par3与PATJ蛋白聚集在上皮细胞周围的功能。
Occludin是一种存在于细胞连接处的细胞膜蛋白。最近的研究发现，occludin还有鲜为人知的一种新功能。这种功能体现在创伤愈合过程中的肾上皮细胞中。研究人员发现，occludin在17小时内能促进90%的细胞完成创口愈合过程。而对occludin进行功能性缺失研究发现，只有28.6%的细胞能完成创口愈合过程。Occludin被发现存在于细胞连接处，促进细胞移行。
研究人员同时发现，aPKC-Par3与PATJ也聚集在移行细胞周围，但是在occludin功能缺失的细胞周围不存在aPKC-Par3/PATJ复合物。细胞移行缺陷的组织失去正常的愈合能力。这些研究数据表明，occludin具有吸引aPKC-Par3/PATJ复合物到移行细胞周围的功能。研究发现occludin具有激活PI3K的功能，PI3K是一种在细胞移行过程中重要的功能酶。
Occludin具有促进aPKC-Par3/PATJ复合物和PI3K的功能，是维持细胞移行的重要蛋白。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
