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.

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和内皮完整性。在这里，我们报告在内皮细胞中，MAGI1 与桩蛋白、β3-整联蛋白、talin 1、张力蛋白 3 和 α-4-辅肌动蛋白共定位于成熟的粘着斑和肌动蛋白应力纤维，并调节它们的动力学。MAGI1 的下调会减少粘着斑形成和成熟、细胞扩散、肌动蛋白应力纤维形成和 RhoA/Rac1 激活。MAGI1 沉默增加了 Y118 处桩蛋白的磷酸化，这是粘着斑周转的指标。MAGI1促进整合素依赖性内皮细胞与ECM的粘附，在体外减少侵袭和小管 生成并在体内抑制血管生成. 我们的结果将 MAGI1 鉴定为粘着斑的新成分，以及粘着斑动力学、细胞粘附、侵袭和血管生成的调节剂。