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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2368-2375. Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2003-12-4430. This Article Full Text (PDF) Erratum (v105,p1395) All Versions of this Article: 2003-12-4430v1 104/8/2368    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 Lau, L.-M. Articles by Jackson, D. E Search for Related Content PubMed PubMed Citation Articles by Lau, L.-M. Articles by Jackson, D. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 30, 2003 Accepted June 7, 2004 The tetraspanin superfamily member, CD151 regulates outside-in integrin IIb3 signalling and platelet function Lai-Man Lau, Janet L Wee, Mark D Wright, Gregory W Moseley, Phillip M Hogarth, Leonie K Ashman, and Denise E Jackson* Austin Hospital, Austin Research Institute, Melbourne, Victoria, Australia School of Biomedical Sciences, University of Newcastle, Callaghan, New South Wales, Australia * Corresponding author; email: d.jackson{at}ari.unimelb.edu.au. The tetraspanin family member, CD151 forms complexes with integrins and regulates cell adhesion and migration. While CD151 is highly expressed in megakaryocytes and to a lesser extent in platelets, its physiologic role in platelets is unclear. In this study, we investigate the physical and functional importance of CD151 in murine platelets. Immunoprecipitation/western blot studies reveal a constitutive physical association of CD151 with integrin IIb3 complex under strong detergent conditions. Using CD151 deficient mice, we show that the platelets have impaired outside-in integrin IIb3 signalling with defective platelet aggregation responses to PAR-4 agonist peptide, collagen and ADP, impaired platelet spreading on fibrinogen and delayed kinetics of clot retraction in vitro. This functional integrin IIb3 defect could not be attributed to altered expression of integrin IIb3. CD151-/- platelets displayed normal platelet alpha granule secretion, dense granule secretion and static platelet adhesion. In addition, CD151-/- platelets displayed normal inside-out integrin IIb3 signalling properties as demonstrated by normal agonist-induced binding of soluble FITC-fibrinogen, JON/A antibody binding, increases in cytosolic free calcium and IP3 levels. This study provides the first direct evidence that CD151 is essential for normal platelet function and that disruption of CD151 induced a moderate outside-in integrin IIb3 signalling defect. 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] P. Gresele, E. Falcinelli, S. Giannini, P. D'Adamo, A. D'Eustacchio, T. Corazzi, A. M. Mezzasoma, F. Di Bari, G. Guglielmini, L. Cecchetti, et al. Dominant inheritance of a novel integrin {beta}3 mutation associated with a hereditary macrothrombocytopenia and platelet dysfunction in two Italian families Haematologica, May 1, 2009; 94(5): 663 - 669. [Abstract] [Full Text] [PDF] G. Baldwin, V. Novitskaya, R. Sadej, E. Pochec, A. Litynska, C. Hartmann, J. Williams, L. Ashman, J. A. Eble, and F. 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