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Blood, 26 February 2009, Vol. 113, No. 9, pp. 2056-2063. Prepublished online as a Blood First Edition Paper on October 2, 2008; DOI 10.1182/blood-2008-07-171611. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-07-171611v1 113/9/2056    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 Braun, A. Articles by Nieswandt, B. Search for Related Content PubMed PubMed Citation Articles by Braun, A. Articles by Nieswandt, B. Related Collections Platelets and Thrombopoiesis Thrombosis and Hemostasis Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Orai1 (CRACM1) is the platelet SOC channel and essential for pathological thrombus formation Attila Braun1,*, David Varga-Szabo1, Christoph Kleinschnitz2, Irina Pleines1, Markus Bender1, Madeleine Austinat2, Michael Bösl3, Guido Stoll2, and Bernhard Nieswandt1,4 1 Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, Würzburg; 2 Department of Neurology, University of Würzburg, Würzburg; 3 Max-Planck-Institute for Biochemistry, Martinsried; and 4 Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany Platelet activation and aggregation at sites of vascular injury are essential for primary hemostasis, but are also major pathomechanisms underlying myocardial infarction and stroke. Changes in [Ca2+]i are a central step in platelet activation. In nonexcitable cells, receptor-mediated depletion of intracellular Ca2+ stores triggers Ca2+ entry through store-operated calcium (SOC) channels. STIM1 has been identified as an endoplasmic reticulum (ER)–resident Ca2+ sensor that regulates store-operated calcium entry (SOCE) in immune cells and platelets, but the identity of the platelet SOC channel has remained elusive. Orai1 (CRACM1) is the recently discovered SOC (CRAC) channel in T cells and mast cells but its role in mammalian physiology is unknown. Here we report that Orai1 is strongly expressed in human and mouse platelets. To test its role in blood clotting, we generated Orai1-deficient mice and found that their platelets display severely defective SOCE, agonist-induced Ca2+ responses, and impaired activation and thrombus formation under flow in vitro. As a direct consequence, Orai1 deficiency in mice results in resistance to pulmonary thromboembolism, arterial thrombosis, and ischemic brain infarction, but only mild bleeding time prolongation. These results establish Orai1 as the long-sought platelet SOC channel and a crucial mediator of ischemic cardiovascular and cerebrovascular events. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Orai1: a channel to safer antithrombotic therapy Kalwant S. Authi Blood 2009 113: 1872-1873. [Full Text] [PDF] This article has been cited by other articles: A. Berna-Erro, A. Braun, R. Kraft, C. Kleinschnitz, M. K. Schuhmann, D. Stegner, T. Wultsch, J. Eilers, S. G. Meuth, G. Stoll, et al. STIM2 Regulates Capacitive Ca2+ Entry in Neurons and Plays a Key Role in Hypoxic Neuronal Cell Death Sci. Signal., October 20, 2009; 2(93): ra67 - ra67. [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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