Gálvez Beatriz G, Matías-Román Salomón, Yáñez-Mó María, Vicente-Manzanares Miguel, Sánchez-Madrid Francisco, Arroyo Alicia G
Departamento de Inmunología, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
Mol Biol Cell. 2004 Feb;15(2):678-87. doi: 10.1091/mbc.e03-07-0516. Epub 2003 Dec 2.
The extracellular matrix (ECM) distinctly modulates membrane type 1-matrix metalloproteinase (MT1-MMP) in human endothelial cells (ECs). Herein, ECM-dependent RhoA activation is shown to regulate MT1-MMP localization and activity as well as clathrin-independent internalization in confluent ECs. In this regard, caveolae are revealed as the major MT1-MMP endocytic pathway in human ECs. Thus, MT1-MMP is present at caveolae with caveolin-1 and both proteins together with alpha v beta 3 integrin colocalize at endothelial motility-associated extensions. Remarkably, caveolae traffic is required for proper MT1-MMP localization, activity, and function in migratory ECs as demonstrated by both treatment with caveolae-disrupting agents or selective targeting caveolin-1 expression by interference RNA. Thus, caveolae-mediated traffic constitutes a novel mechanism for MT1-MMP regulation in ECs during angiogenesis.
细胞外基质（ECM）对人内皮细胞（ECs）中的膜型1基质金属蛋白酶（MT1-MMP）具有显著的调节作用。本文表明，ECM依赖性RhoA激活可调节汇合ECs中MT1-MMP的定位、活性以及网格蛋白非依赖性内化。在这方面，小窝被揭示为人ECs中MT1-MMP的主要内吞途径。因此，MT1-MMP与小窝蛋白-1共同存在于小窝中，这两种蛋白与αvβ3整合素一起在内皮细胞运动相关的延伸部位共定位。值得注意的是，小窝运输对于迁移ECs中MT1-MMP的正确定位、活性和功能是必需的，这一点通过用小窝破坏剂处理或通过干扰RNA选择性靶向小窝蛋白-1表达得以证明。因此，小窝介导的运输构成了血管生成过程中ECs中MT1-MMP调节的一种新机制。
