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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 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 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 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. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Cytoskeleton Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The tetraspanin superfamily member CD151 regulates outside-in integrin IIb3 signaling and platelet function Lai-Man Lau, Janet L. Wee, Mark D. Wright, Gregory W. Moseley, P. Mark Hogarth, Leonie K. Ashman, and Denise E. Jackson From the Kronheimer Building, Austin Research Institute, Austin Hospital, Heidelberg, Australia; and the School of Biomedical Sciences, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia. 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 signaling with defective platelet aggregation responses to protease-activated receptor 4 (PAR-4) agonist peptide, collagen, and adenosine diphosphate (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 signaling properties as demonstrated by normal agonist-induced binding of soluble fluorescein isothiocyanate (FITC)–fibrinogen, JON/A antibody binding, and increases in cytosolic-free calcium and inositol 1,4,5 triphosphate (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 signaling defect. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Baldwin, V. Novitskaya, R. Sadej, E. Pochec, A. Litynska, C. Hartmann, J. Williams, L. Ashman, J. A. Eble, and F. Berditchevski Tetraspanin CD151 Regulates Glycosylation of {alpha}3{beta}1 Integrin J. Biol. Chem., December 19, 2008; 283(51): 35445 - 35454. [Abstract] [Full Text] [PDF] X. H. Yang, A. L. Richardson, M. I. Torres-Arzayus, P. Zhou, C. Sharma, A. R. Kazarov, M. M. Andzelm, J. L. Strominger, M. Brown, and M. E. Hemler CD151 Accelerates Breast Cancer by Regulating {alpha}6 Integrin Function, Signaling, and Molecular Organization Cancer Res., May 1, 2008; 68(9): 3204 - 3213. [Abstract] [Full Text] [PDF] C. V. Denis and D. D. Wagner Platelet Adhesion Receptors and Their Ligands in Mouse Models of Thrombosis Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 728 - 739. [Abstract] [Full Text] [PDF] Y. Takeda, A. R. Kazarov, C. E. Butterfield, B. D. Hopkins, L. E. Benjamin, A. Kaipainen, and M. E. Hemler Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro Blood, February 15, 2007; 109(4): 1524 - 1532. [Abstract] [Full Text] [PDF] M. W. Goschnick, L.-M. Lau, J. L. Wee, Y. S. Liu, P. M. Hogarth, L. M. Robb, M. J. Hickey, M. D. Wright, and D. E. Jackson Impaired "outside-in" integrin {alpha}IIbbeta3 signaling and thrombus stability in TSSC6-deficient mice Blood, September 15, 2006; 108(6): 1911 - 1918. [Abstract] [Full Text] [PDF] I.-K. Hong, Y.-J. Jin, H.-J. Byun, D.-I. Jeoung, Y.-M. Kim, and H. Lee Homophilic Interactions of Tetraspanin CD151 Up-regulate Motility and Matrix Metalloproteinase-9 Expression of Human Melanoma Cells through Adhesion-dependent c-Jun Activation Signaling Pathways J. Biol. Chem., August 25, 2006; 281(34): 24279 - 24292. [Abstract] [Full Text] [PDF] S. Gesierich, I. Berezovskiy, E. Ryschich, and M. Zoller Systemic Induction of the Angiogenesis Switch by the Tetraspanin D6.1A/CO-029. Cancer Res., July 15, 2006; 66(14): 7083 - 7094. [Abstract] [Full Text] [PDF] M. Sala-Valdes, A. Ursa, S. Charrin, E. Rubinstein, M. E. Hemler, F. Sanchez-Madrid, and M. Yanez-Mo EWI-2 and EWI-F Link the Tetraspanin Web to the Actin Cytoskeleton through Their Direct Association with Ezrin-Radixin-Moesin Proteins J. Biol. Chem., July 14, 2006; 281(28): 19665 - 19675. [Abstract] [Full Text] [PDF] J. L. Wee and D. E. Jackson The Ig-ITIM superfamily member PECAM-1 regulates the "outside-in" signaling properties of integrin {alpha}IIb{beta}3 in platelets Blood, December 1, 2005; 106(12): 3816 - 3823. [Abstract] [Full Text] [PDF] F. Martin, D. M. Roth, D. A. Jans, C. W. Pouton, L. J. Partridge, P. N. Monk, and G. W. Moseley Tetraspanins in Viral Infections: a Fundamental Role in Viral Biology? J. Virol., September 1, 2005; 79(17): 10839 - 10851. [Full Text] [PDF] O. Barreiro, M. Yanez-Mo, M. Sala-Valdes, M. D. Gutierrez-Lopez, S. Ovalle, A. Higginbottom, P. N. Monk, C. Cabanas, and F. Sanchez-Madrid Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation Blood, April 1, 2005; 105(7): 2852 - 2861. [Abstract] [Full Text] [PDF] R. Nishiuchi, N. Sanzen, S. Nada, Y. Sumida, Y. Wada, M. Okada, J. Takagi, H. Hasegawa, and K. 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