An EF hand mutation in Stim1 causes premature platelet activation and bleeding in mice.
J Clin Invest
; 117(11): 3540-50, 2007 Nov.
Article
en En
| MEDLINE
| ID: mdl-17965774
ABSTRACT
Changes in cytoplasmic Ca2+ levels regulate a variety of fundamental cellular functions in virtually all cells. In nonexcitable cells, a major pathway of Ca2+ entry involves receptor-mediated depletion of intracellular Ca2+ stores followed by the activation of store-operated calcium channels in the plasma membrane. We have established a mouse line expressing an activating EF hand motif mutant of stromal interaction molecule 1 (Stim1), an ER receptor recently identified as the Ca2+ sensor responsible for activation of Ca2+ release-activated (CRAC) channels in T cells, whose function in mammalian physiology is not well understood. Mice expressing mutant Stim1 had macrothrombocytopenia and an associated bleeding disorder. Basal intracellular Ca2+ levels were increased in platelets, which resulted in a preactivation state, a selective unresponsiveness to immunoreceptor tyrosine activation motif-coupled agonists, and increased platelet consumption. In contrast, basal Ca2+ levels, but not receptor-mediated responses, were affected in mutant T cells. These findings identify Stim1 as a central regulator of platelet function and suggest a cell type-specific activation or composition of the CRAC complex.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trombocitopenia
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Glicoproteínas de Membrana
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Activación Plaquetaria
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Calcio
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Motivos EF Hand
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Hemorragia
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Mutación
Tipo de estudio:
Etiology_studies
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Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2007
Tipo del documento:
Article