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MAGI1 定位于成熟的焦点黏附,并调节内皮细胞黏附、迁移和血管生成。

MAGI1 localizes to mature focal adhesion and modulates endothelial cell adhesion, migration and angiogenesis.

机构信息

Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland.

Westmead Institute for Medical Research, University of Sydney, Sydney, Australia.

出版信息

Cell Adh Migr. 2021 Dec;15(1):126-139. doi: 10.1080/19336918.2021.1911472.

Abstract

MAGI1 is an intracellular adaptor protein that stabilizes cell junctions and regulates epithelial and endothelial integrity. Here, we report that that in endothelial cells MAGI1 colocalizes with paxillin, β3-integrin, talin 1, tensin 3 and α-4-actinin at mature focal adhesions and actin stress fibers, and regulates their dynamics. Downregulation of MAGI1 reduces focal adhesion formation and maturation, cell spreading, actin stress fiber formation and RhoA/Rac1 activation. MAGI1 silencing increases phosphorylation of paxillin at Y118, an indicator of focal adhesion turnover. MAGI1 promotes integrin-dependent endothelial cells adhesion to ECM, reduces invasion and tubulogenesis and suppresses angiogenesis  . Our results identify MAGI1 as anovel component of focal adhesions, and regulator of focal adhesion dynamics, cell adhesion, invasion and angiogenesis.

摘要

MAGI1 是一种细胞内衔接蛋白,可稳定细胞连接并调节上皮细胞和内皮细胞的完整性。在这里,我们报告 MAGI1 在成熟的黏着斑和肌动蛋白应力纤维上与粘着斑蛋白、β3-整合素、talin1、tensin3 和 α-4-辅肌动蛋白共定位,并调节其动态变化。MAGI1 的下调会减少黏着斑的形成和成熟、细胞铺展、肌动蛋白应力纤维的形成以及 RhoA/Rac1 的激活。MAGI1 沉默会增加 Y118 位点粘着斑蛋白的磷酸化,这是黏着斑周转率的一个指标。MAGI1 促进整合素依赖性内皮细胞黏附到细胞外基质,减少侵袭和管状形成,并抑制血管生成。我们的研究结果表明 MAGI1 是黏着斑的一个新组成部分,也是黏着斑动态、细胞黏附、侵袭和血管生成的调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf2d/8115569/342dea16e7ba/KCAM_A_1911472_F0001_OC.jpg

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