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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3217-3226. Prepublished online as a Blood First Edition Paper on July 28, 2008; DOI 10.1182/blood-2008-02-139394. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-02-139394v1 112/8/3217    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yañez-Mó, M. Articles by Sánchez-Madrid, F. Search for Related Content PubMed PubMed Citation Articles by Yañez-Mó, M. Articles by Sánchez-Madrid, F. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells María Yañez-Mó1,2, Olga Barreiro2, Pilar Gonzalo2, Alicia Batista3, Diego Megías4, Laura Genís2, Norman Sachs5, Mónica Sala-Valdés2, Miguel A. Alonso3, María C. Montoya4, Arnoud Sonnenberg5, Alicia G. Arroyo2, and Francisco Sánchez-Madrid1,2 1 Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain; 2 Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; 3 Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Consejo Superior de Investigaciones Científicas, Madrid, Spain; 4 Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; and 5 Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands MT1-MMP plays a key role in endothelial function, as underscored by the angiogenic defects found in MT1-MMP deficient mice. We have studied the molecular interactions that underlie the functional regulation of MT1-MMP. At lateral endothelial cell junctions, MT1-MMP colocalizes with tetraspanin CD151 (Tspan 24) and its associated partner 3β1 integrin. Biochemical and FRET analyses show that MT1-MMP, through its hemopexin domain, associates tightly with CD151, thus forming 3β1 integrin/CD151/MT1-MMP ternary complexes. siRNA knockdown of HUVEC CD151 expression enhanced MT1-MMP-mediated activation of MMP2, and the same activation was seen in ex vivo lung endothelial cells isolated from CD151-deficient mice. However, analysis of collagen degradation in these experimental models revealed a diminished MT1-MMP enzymatic activity in confined areas around the cell periphery. CD151 knockdown affected both MT1-MMP subcellular localization and its inclusion into detergent-resistant membrane domains, and prevented biochemical association of the metalloproteinase with the integrin 3β1. These data provide evidence for a novel regulatory role of tetraspanin microdomains on the collagenolytic activity of MT1-MMP and indicate that CD151 is a key regulator of MT1-MMP in endothelial homeostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Zhang, J. Kotha, L. K. Jennings, and X. A. Zhang Tetraspanins and vascular functions Cardiovasc Res, July 1, 2009; 83(1): 7 - 15. [Abstract] [Full Text] [PDF] M. A. Lafleur, D. Xu, and M. E. Hemler Tetraspanin Proteins Regulate Membrane Type-1 Matrix Metalloproteinase-dependent Pericellular Proteolysis Mol. Biol. Cell, April 1, 2009; 20(7): 2030 - 2040. [Abstract] [Full Text] [PDF]

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