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

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 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.

Keywords

• cell adhesion
• migration
• signaling
• extracellular matrix
• cytoskeleton
• stress fibers