title: Caveolae are a novel pathway for membrane-type 1 matrix metalloproteinase traffic in human endothelial cells.
abstract: 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.
authors.affiliation: Departamento de Inmunología, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Gálvez
authors.forename: Salomón
authors.initials: S
authors.lastname: Matías-Román
authors.forename: María
authors.initials: M
authors.lastname: Yáñez-Mó
authors.forename: Miguel
authors.initials: M
authors.lastname: Vicente-Manzanares
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.forename: Alicia G
authors.initials: AG
authors.lastname: Arroyo
mesh_terms: 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*
chemical_list: 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