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Background

Stromal interaction molecule 1 (STIM1) was recently identified as a critical component of store-operated calcium entry (SOCE) in platelets. We previously reported the Ca(2+) -sensing guanine nucleotide exchange factor CalDAG-GEFI as a critical molecule in Ca(2+) signaling in platelets.

Objective

To evaluate the contribution of STIM1/SOCE to Ca(2+) -dependent platelet activation and thrombosis, we here compared the activation responses of platelets lacking STIM1 and platelets lacking CalDAG-GEFI.

Methods

The murine Stim1 gene was conditionally deleted in the megakaryocyte/platelet lineage. CalDAG-GEFI(-/-) and Stim1(fl/fl) PF4-Cre mice, along with littermate control mice, were used for in vitro and in vivo experiments under flow as well as static conditions.

Results

Integrin α(IIb) β(3) -mediated aggregation was markedly impaired in CalDAG-GEFI-deficient but not STIM1-deficient platelets, under both static and flow conditions. In contrast, deficiency in either STIM1 or CalDAG-GEFI significantly impaired the ability of platelets to express phosphatidylserine on the cell surface. When subjected to a laser injury thrombosis model, mice lacking STIM1 in platelets were characterized by the formation of unstable platelet-rich thrombi and delayed and reduced fibrin generation in injured arterioles. In CalDAG-GEFI(-/-) mice, fibrin generation was also delayed and reduced, but platelet accumulation was almost abolished.

Conclusions

Our studies suggest that: (i) STIM1/SOCE is critical for the procoagulant activity but not the proadhesive function of platelets; and (ii) at the site of vascular injury, STIM1 and CalDAG-GEFI are critical for the first wave of thrombin generation mediated by procoagulant platelets."xsd:string
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http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/author"Ahmad F."xsd:string
http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/author"Bergmeier W."xsd:string
http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/author"Feske S."xsd:string
http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/author"Poncz M."xsd:string
http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/author"Boulaftali Y."xsd:string
http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/author"Greene T.K."xsd:string
http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/author"Ouellette T.D."xsd:string
http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/name"J Thromb Haemost"xsd:string
http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/pages"2077-2086"xsd:string
http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/title"Relative contributions of stromal interaction molecule 1 and CalDAG-GEFI to calcium-dependent platelet activation and thrombosis."xsd:string
http://purl.uniprot.org/citations/21848641http://purl.uniprot.org/core/volume"9"xsd:string
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