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PMID: 14657245 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Molecular biology of the cell ·Vol. 15 ·No. 2 ·2004-02-00 ·Pages 678-87

Gálvez BG, Matías-Román S, Yáñez-Mó M, Vicente-Manzanares M, Sánchez-Madrid F, Arroyo AG

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.

MeSH Terms
Caveolae/drug effects,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 RNA, Small Interfering/metabolism rhoA GTP-Binding Protein/metabolism
Chemicals
CAV1 protein, human Caveolin 1 Caveolins Integrin alphaVbeta3 RNA, Small Interfering Filipin Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases rhoA GTP-Binding Protein
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Gálvez Beatriz G
Departamento de Inmunología, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
Matías-Román Salomón
Yáñez-Mó María
Vicente-Manzanares Miguel
Sánchez-Madrid Francisco
Arroyo Alicia G
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e03-07-0516
Published
2004-02-00
Epub
2003-00-02
Pages
678-87
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC329288
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e03-07-0516 PMC Full Text View journal details
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