R93W mutation in Orai1 causes impaired calcium influx in platelets

Wolfgang Bergmeier, Oh Hora Masatsugu, Christie Ann McCarl, R. Claire Roden, Paul F. Bray, Stefan Feske

    Research output: Contribution to journalArticle

    96 Citations (Scopus)

    Abstract

    The intracellular Ca 2+concentration of many nonexcitable 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 endoplasmic 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 (Orai1 R93W). Platelets expressing Orai1 R93W were characterized by markedly reduced SOCE and impaired agonistinduced increases in [Ca 2+]i. Orai1 R93W 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 Orai1 R93W platelets to aggregate or to adhere to collagen under arterial flow conditions ex vivo. In contrast, these adherent Orai1 R93W platelets were defective in surface phosphatidylserine exposure, suggesting that Orai1 is crucial for the platelets' procoagulant response rather than for other Ca 2+-dependent cellular responses.

    Original languageEnglish
    Pages (from-to)675-678
    Number of pages4
    JournalBlood
    Volume113
    Issue number3
    DOIs
    Publication statusPublished - Jan 15 2009

    Fingerprint

    Platelets
    Blood Platelets
    Calcium
    Mutation
    Cells
    Phosphatidylserines
    Integrins
    Endoplasmic Reticulum
    Blood Cells
    Blood
    Collagen
    Chemical activation
    Defects
    Sensors

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

    Cite this

    Bergmeier, W., Masatsugu, O. H., McCarl, C. A., Roden, R. C., Bray, P. F., & Feske, S. (2009). R93W mutation in Orai1 causes impaired calcium influx in platelets. Blood, 113(3), 675-678. https://doi.org/10.1182/blood-2008-08-174516

    R93W mutation in Orai1 causes impaired calcium influx in platelets. / Bergmeier, Wolfgang; Masatsugu, Oh Hora; McCarl, Christie Ann; Roden, R. Claire; Bray, Paul F.; Feske, Stefan.

    In: Blood, Vol. 113, No. 3, 15.01.2009, p. 675-678.

    Research output: Contribution to journalArticle

    Bergmeier, W, Masatsugu, OH, McCarl, CA, Roden, RC, Bray, PF & Feske, S 2009, 'R93W mutation in Orai1 causes impaired calcium influx in platelets', Blood, vol. 113, no. 3, pp. 675-678. https://doi.org/10.1182/blood-2008-08-174516
    Bergmeier W, Masatsugu OH, McCarl CA, Roden RC, Bray PF, Feske S. R93W mutation in Orai1 causes impaired calcium influx in platelets. Blood. 2009 Jan 15;113(3):675-678. https://doi.org/10.1182/blood-2008-08-174516
    Bergmeier, Wolfgang ; Masatsugu, Oh Hora ; McCarl, Christie Ann ; Roden, R. Claire ; Bray, Paul F. ; Feske, Stefan. / R93W mutation in Orai1 causes impaired calcium influx in platelets. In: Blood. 2009 ; Vol. 113, No. 3. pp. 675-678.
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