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

被引:14
作者
Alday-Parejo, Begona [1 ]
Ghimire, Kedar [1 ,2 ]
Coquoz, Oriana [1 ]
Albisetti, Gioele W. [1 ,3 ]
Tamo, Luca [1 ,4 ]
Zaric, Jelena [1 ,5 ]
Stalin, Jimmy [1 ]
Ruegg, Curzio [1 ]
机构
[1] Univ Fribourg, Fac Sci & Med, Dept Oncol Microbiol & Immunol, Lab Expt & Translat Oncol,Pathol, Chemin Musee 18,17, CH-1700 Fribourg, Switzerland
[2] Univ Sydney, Westmead Inst Med Res, Sydney, NSW, Australia
[3] Univ Zurich, Inst Pharmacol & Toxicol, Sect Neuropharmacol, Zurich, Switzerland
[4] Univ Bern, Clin Trials Unit, Bern, Switzerland
[5] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res, Lausanne, Switzerland
基金
瑞士国家科学基金会;
关键词
Cell adhesion; migration; signaling; extracellular matrix; cytoskeleton; stress fibers;
D O I
10.1080/19336918.2021.1911472
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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, beta 3-integrin, talin 1, tensin 3 and alpha-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 tubulogenesisin vitro and suppresses angiogenesis in vivo. Our results identify MAGI1 as anovel component of focal adhesions, and regulator of focal adhesion dynamics, cell adhesion, invasion and angiogenesis.
引用
收藏
页码:126 / 139
页数:14
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