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Blood, 15 January 2009, Vol. 113, No. 3, pp. 675-678. Prepublished online as a Blood First Edition Paper on October 24, 2008; DOI 10.1182/blood-2008-08-174516. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-08-174516v1 113/3/675    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 Bergmeier, W. Articles by Feske, S. Search for Related Content PubMed PubMed Citation Articles by Bergmeier, W. Articles by Feske, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 19, 2008 Accepted October 13, 2008 R93W mutation in Orai1 causes impaired calcium influx in platelets Wolfgang Bergmeier*, Masatsugu Oh-hora, Christie-Ann McCarl, R. Claire Roden, Paul F. Bray, and Stefan Feske Immune Disease Institute and Harvard Medical School, Boston, MA, United States Department of Pathology, New York University School of Medicine, New York, NY, United States Cardeza Foundation and Department of Medicine, Thomas Jefferson University, Philadelphia, PA, United States * Corresponding author; email: wolfgang.bergmeier{at}jefferson.edu. The intracellular Ca2+ concentration of non-excitable cells is regulated by calcium store release and store-operated calcium entry (SOCE). In platelets, STIM1 was recently identified as the main calcium sensor expressed in the endoplasmatic reticulum. To evaluate the role of the SOC channel moiety, Orai1, in platelet SOCE, we generated mice expressing a mutated, inactive form of Orai1 in blood cells only (Orai1R93W). Platelets expressing Orai1R93W were characterized by markedly reduced SOCE and impaired agonist-induced increases in [Ca2+]i . Orai1R93W platelets showed reduced integrin activation and impaired degranulation when stimulated with low agonist concentrations under static conditions. This defect, however, did not significantly affect the ability of Orai1R93W platelets to aggregate or to adhere to collagen under arterial flow conditions ex vivo. In contrast, these adherent Orai1R93W platelets were defective in surface phosphatidylserine exposure, suggesting that Orai1 is crucial for the platelets pro-coagulant response rather than for other Ca2+-dependent cellular responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Derler, M. Fahrner, O. Carugo, M. Muik, J. Bergsmann, R. Schindl, I. Frischauf, S. Eshaghi, and C. Romanin Increased Hydrophobicity at the N Terminus/Membrane Interface Impairs Gating of the Severe Combined Immunodeficiency-related ORAI1 Mutant J. Biol. Chem., June 5, 2009; 284(23): 15903 - 15915. [Abstract] [Full Text] [PDF] K. S. Authi Orai1: a channel to safer antithrombotic therapy Blood, February 26, 2009; 113(9): 1872 - 1873. [Full Text] [PDF]

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