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Blood, 15 September 2006, Vol. 108, No. 6, pp. 1911-1918. Prepublished online as a Blood First Edition Paper on May 23, 2006; DOI 10.1182/blood-2006-02-004267. This Article Full Text (PDF) All Versions of this Article: blood-2006-02-004267v1 108/6/1911    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 Goschnick, M. W Articles by Jackson, D. E Search for Related Content PubMed PubMed Citation Articles by Goschnick, M. W Articles by Jackson, D. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 16, 2006 Accepted May 9, 2006 Impaired 'outside-in' integrin IIb3 signaling and thrombus stability in TSSC6-deficient mice Matt W Goschnick, Lai-Man Lau, Janet L Wee, Yong S Liu, P M Hogarth, Lorraine M Robb, Michael J Hickey, Mark D Wright, and Denise E Jackson* Kronheimer Building,Burnet Institute Incorporating the Austin Research Institute,Victoria,Australia The Walter and Eliza Hall Institute, Parkville, Victoria, Australia Centre for Inflammatory Diseases, Department of Medicine, Monash University, Victoria, Australia * Corresponding author; email: d.jackson{at}burnet.edu.au. We investigated the role of the hematopoietic specific tetraspanin superfamily member, TSSC6, in platelet function using wild-type mice and TSSC6 deficient mice. TSSC6 is expressed on the surface of murine platelets and is upregulated by thrombin stimulation, indicating an intracellular pool of TSSC6. Immunoprecipitation/western blot studies reveal a constitutive physical association of TSSC6 with integrin IIb3 complex under strong detergent conditions. In vivo evaluation of hemostasis by tail bleeding revealed increased bleeding time, volume of blood lost, and evidence of tail rebleeds in TSSC6 null mice indicating unstable haemostasis. Using ex vivo techniques, we showed that TSSC6-deficient platelets exhibited impaired kinetics of clot retraction, platelet aggregation at lower doses of PAR-4 and collagen and platelet spreading on fibrinogen in the presence of normal integrin IIb3 expression. TSSC6-deficient platelets showed normal alpha granule secretion, normal 'inside-out' integrin IIb3 signaling (FITC-fibrinogen and JON/A binding), and normal platelet adhesion on fibrinogen. Furthermore, we show that absence of platelet TSSC6 affects the secondary stability of arterial thrombi in vivo upon vascular injury. These data demonstrate that TSSC6 appears to regulate integrin IIb3 'outside-in' signaling events in platelets and is necessary for stability of arterial thrombi in vivo. 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] C. Wong, Y. Liu, J. Yip, R. Chand, J. L. Wee, L. Oates, B. Nieswandt, A. Reheman, H. Ni, N. Beauchemin, et al. CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo Blood, February 19, 2009; 113(8): 1818 - 1828. [Abstract] [Full Text] [PDF] J. Schroder, R. Lullmann-Rauch, N. Himmerkus, I. Pleines, B. Nieswandt, Z. Orinska, F. Koch-Nolte, B. Schroder, M. Bleich, and P. Saftig Deficiency of the Tetraspanin CD63 Associated with Kidney Pathology but Normal Lysosomal Function Mol. Cell. 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