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Kindlin-2招募桩蛋白和肌动蛋白相关蛋白2/3，以在细胞初始铺展过程中促进膜突出。

Kindlin-2 recruits paxillin and Arp2/3 to promote membrane protrusions during initial cell spreading.

作者信息

Böttcher Ralph T, Veelders Maik, Rombaut Pascaline, Faix Jan, Theodosiou Marina, Stradal Theresa E, Rottner Klemens, Zent Roy, Herzog Franz, Fässler Reinhard

机构信息

Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany

German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.

出版信息

J Cell Biol. 2017 Nov 6;216(11):3785-3798. doi: 10.1083/jcb.201701176. Epub 2017 Sep 14.

DOI:10.1083/jcb.201701176
PMID:28912124
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5674885/
Abstract

Cell spreading requires the coupling of actin-driven membrane protrusion and integrin-mediated adhesion to the extracellular matrix. The integrin-activating adaptor protein kindlin-2 plays a central role for cell adhesion and membrane protrusion by directly binding and recruiting paxillin to nascent adhesions. Here, we report that kindlin-2 has a dual role during initial cell spreading: it binds paxillin via the pleckstrin homology and F0 domains to activate Rac1, and it directly associates with the Arp2/3 complex to induce Rac1-mediated membrane protrusions. Consistently, abrogation of kindlin-2 binding to Arp2/3 impairs lamellipodia formation and cell spreading. Our findings identify kindlin-2 as a key protein that couples cell adhesion by activating integrins and the induction of membrane protrusions by activating Rac1 and supplying Rac1 with the Arp2/3 complex.

摘要

细胞铺展需要肌动蛋白驱动的膜突起与整合素介导的细胞外基质黏附相耦合。整合素激活衔接蛋白纽带蛋白-2通过直接结合并将桩蛋白招募至新生黏附位点，在细胞黏附和膜突起过程中发挥核心作用。在此，我们报道纽带蛋白-2在细胞铺展初期具有双重作用：它通过pleckstrin同源结构域和F0结构域结合桩蛋白以激活Rac1，并且它直接与Arp2/3复合体结合以诱导Rac1介导的膜突起。一致地，纽带蛋白-2与Arp2/3结合的缺失会损害片状伪足的形成和细胞铺展。我们的研究结果确定纽带蛋白-2是一种关键蛋白，它通过激活整合素实现细胞黏附，并通过激活Rac1和为Rac1提供Arp2/3复合体来诱导膜突起。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/2daf88e46b55/JCB_201701176_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/dcc76907c628/JCB_201701176_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/0c1d6c2c4891/JCB_201701176_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/2cda16742ceb/JCB_201701176_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/e2cc96f4d142/JCB_201701176_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/76932a0bac8d/JCB_201701176_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/2daf88e46b55/JCB_201701176_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/dcc76907c628/JCB_201701176_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/0c1d6c2c4891/JCB_201701176_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/2cda16742ceb/JCB_201701176_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/e2cc96f4d142/JCB_201701176_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/76932a0bac8d/JCB_201701176_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddb/5674885/2daf88e46b55/JCB_201701176_Fig6.jpg

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