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 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.
Gálvez
Beatriz G
BG
Departamento de Inmunología, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
Matías-Román
Salomón
S
Yáñez-Mó
María
M
Vicente-Manzanares
Miguel
M
Sánchez-Madrid
Francisco
F
Arroyo
Alicia G
AG
D021941:Caveolae / Q000187:drug effects / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005372:Filipin / Q000494:pharmacology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D021381:Protein Transport / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D039302:Integrin alphaVbeta3; D034741:RNA, Small Interfering; D005372:Filipin; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020742:rhoA GTP-Binding Protein