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 (US)
Pages (from-to)675-678
Number of pages4
JournalBlood
Volume113
Issue number3
DOIs
StatePublished - Jan 15 2009

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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
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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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

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

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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