R93W mutation in Orai1 causes impaired calcium influx in platelets

被引:99
作者
Bergmeier, Wolfgang [1 ,2 ,3 ,4 ]
Oh-hora, Masatsugu [2 ,3 ]
McCarl, Christie-Ann [2 ,3 ,5 ]
Roden, R. Claire [1 ,4 ]
Bray, Paul F. [1 ,4 ]
Feske, Stefan [2 ,3 ,5 ]
机构
[1] Thomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19007 USA
[2] Immune Dis Inst, Boston, MA USA
[3] Harvard Univ, Sch Med, Boston, MA USA
[4] Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19007 USA
[5] NYU, Sch Med, New York, NY USA
基金
美国国家卫生研究院;
关键词
CHANNEL FUNCTION; CA2+ CHANNELS; SENSOR STIM1; MICE LACKING; CRAC CHANNEL; ACTIVATION; ENTRY; CELL; INHIBITION; DEFICIENCY;
D O I
10.1182/blood-2008-08-174516
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 Orai1R93W were characterized by markedly reduced SOCE and impaired agonist-induced 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. (Blood. 2009; 113: 675-678)
引用
收藏
页码:675 / 678
页数:4
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