Caveolae are a novel pathway for membrane-type 1 matrix metalloproteinase traffic in human endothelial cells

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 t...

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Published in:Molecular biology of the cell 2004-02, Vol.15 (2), p.678-687
Main Authors: Gálvez, Beatriz G, Matías-Román, Salomón, Yáñez-Mó, María, Vicente-Manzanares, Miguel, Sánchez-Madrid, Francisco, Arroyo, Alicia G
Format: Article
Language:English
Subjects:
Caveolae - drug effects
Caveolae - metabolism
Caveolin 1
Caveolins - metabolism
Cells, Cultured
Endothelial Cells - metabolism
Extracellular Matrix - metabolism
Filipin - pharmacology
Humans
Integrin alphaVbeta3 - metabolism
Matrix Metalloproteinases, Membrane-Associated
Metalloendopeptidases - metabolism
Neovascularization, Physiologic
Protein Transport - physiology
rhoA GTP-Binding Protein - metabolism
RNA, Small Interfering - metabolism
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Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E03-07-0516