R93W mutation in Orai1 causes impaired calcium influx in platelets
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作者:
Bergmeier, Wolfgang
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Thomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19007 USA
Immune Dis Inst, Boston, MA USA
Harvard Univ, Sch Med, Boston, MA USA
Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19007 USAThomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19007 USA
Bergmeier, Wolfgang
[1
,2
,3
,4
]
Oh-hora, Masatsugu
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机构:
Immune Dis Inst, Boston, MA USA
Harvard Univ, Sch Med, Boston, MA USAThomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19007 USA
Oh-hora, Masatsugu
[2
,3
]
McCarl, Christie-Ann
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机构:
Immune Dis Inst, Boston, MA USA
Harvard Univ, Sch Med, Boston, MA USA
NYU, Sch Med, New York, NY USAThomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19007 USA
McCarl, Christie-Ann
[2
,3
,5
]
Roden, R. Claire
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机构:
Thomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19007 USA
Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19007 USAThomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19007 USA
Roden, R. Claire
[1
,4
]
Bray, Paul F.
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Thomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19007 USA
Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19007 USAThomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19007 USA
Bray, Paul F.
[1
,4
]
Feske, Stefan
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Immune Dis Inst, Boston, MA USA
Harvard Univ, Sch Med, Boston, MA USA
NYU, Sch Med, New York, NY USAThomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19007 USA
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
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)
机构:
Univ Oklahoma, Hlth Sci Ctr, Dept Med, WK Warren Med Res Inst, Oklahoma City, OK 73104 USAUniv Oklahoma, Hlth Sci Ctr, Dept Med, WK Warren Med Res Inst, Oklahoma City, OK 73104 USA
机构:
NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USANIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA
DeHaven, Wayne I.
Smyth, Jeremy T.
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NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USANIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA
Smyth, Jeremy T.
Boyles, Rebecca R.
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NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USANIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA
Boyles, Rebecca R.
Putney, James W., Jr.
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NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USANIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA
机构:
Univ Oklahoma, Hlth Sci Ctr, Dept Med, WK Warren Med Res Inst, Oklahoma City, OK 73104 USAUniv Oklahoma, Hlth Sci Ctr, Dept Med, WK Warren Med Res Inst, Oklahoma City, OK 73104 USA
机构:
NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USANIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA
DeHaven, Wayne I.
Smyth, Jeremy T.
论文数: 0引用数: 0
h-index: 0
机构:
NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USANIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA
Smyth, Jeremy T.
Boyles, Rebecca R.
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机构:
NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USANIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA
Boyles, Rebecca R.
Putney, James W., Jr.
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h-index: 0
机构:
NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USANIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA