Caveolae are a novel pathway for membrane-type 1 matrix metalloproteinase traffic in human endothelial cells
Caveolae are a novel pathway for membrane-type 1 matrix metalloproteinase traffic in human endothelial cells
复制标题
DOI：
10.1091/mbc.e03-07-0516
复制
发表时间：
2004-02-01
影响因子：
3.3
通讯作者：
Arroyo, AG
中科院分区：
文献类型：
--
作者：
Gálvez, BG;Matías-Román, S;Arroyo, AG
细胞外基质 (ECM) 明显调节人内皮细胞 (EC) 中的膜 1 型基质金属蛋白酶 (MT1-MMP)。在此，ECM 依赖性 RhoA 激活可调节汇合 EC 中 MT1-MMP 的定位和活性以及网格蛋白独立的内化。在这方面，小凹被揭示为人类 EC 中主要的 MT1-MMP 内吞途径。因此，MT1-MMP 与 Caveolin-1 一起存在于小窝中，并且这两种蛋白与 alphavbeta3 整联蛋白一起共定位于内皮运动相关的延伸。值得注意的是，小凹交通对于迁移 EC 中 MT1-MMP 的正确定位、活性和功能是必需的，这一点通过小凹破坏剂的治疗或通过干扰 RNA 选择性靶向 Caveolin-1 表达来证明。因此，小凹介导的交通构成了血管生成过程中 EC 中 MT1-MMP 调节的新机制。
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 alphavbeta3 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.