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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 (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 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 Yanez-Mo, M. Articles by Sanchez-Madrid, F. Search for Related Content PubMed PubMed Citation Articles by Yanez-Mo, M. Articles by Sanchez-Madrid, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 15, 2008 Accepted July 11, 2008 MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells Maria Yanez-Mo, Olga Barreiro, Pilar Gonzalo, Alicia Batista, Diego Megias, Laura Genis, Norman Sachs, Monica Sala-Valdes, Miguel A Alonso, Maria C Montoya, Arnoud Sonnenberg, Alicia G Arroyo, and Francisco Sanchez-Madrid* Servicio de Inmunologia, Hospital de la Princesa, Universidad Autonoma de Madrid, Madrid, Spain Vascular Biology and Inflammation department, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain Centro de Biologia Molecular Severo Ochoa, CBMSO-UAM, Madrid, Spain Centro Nacional de Investigaciones Oncologicas, Madrid, Spain Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, Netherlands * Corresponding author; email: fsanchez.hlpr{at}salud.madrid.org. 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 31 integrin. Biochemical and FRET analyses show that MT1-MMP, through its hemopexin domain, associates tightly with CD151, thus forming 31 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 knock down affected both MT1-MMP subcellular localization and its inclusion into detergent-resistant membrane domains, and prevented biochemical association of the metalloproteinase with the integrin 31 . 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] O. Barreiro, M. Zamai, M. Yanez-Mo, E. Tejera, P. Lopez-Romero, P. N. Monk, E. Gratton, V. R. Caiolfa, and F. Sanchez-Madrid Endothelial adhesion receptors are recruited to adherent leukocytes by inclusion in preformed tetraspanin nanoplatforms J. Cell Biol., November 3, 2008; 183(3): 527 - 542. [Abstract] [Full Text] [PDF]

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