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Publication : Syntaxin 8 regulates platelet dense granule secretion, aggregation, and thrombus stability.

First Author  Golebiewska EM Year  2015
Journal  J Biol Chem Volume  290
Issue  3 Pages  1536-45
PubMed ID  25404741 Mgi Jnum  J:218388
Mgi Id  MGI:5617412 Doi  10.1074/jbc.M114.602615
Citation  Golebiewska EM, et al. (2015) Syntaxin 8 regulates platelet dense granule secretion, aggregation, and thrombus stability. J Biol Chem 290(3):1536-45
abstractText  Platelet secretion not only drives thrombosis and hemostasis, but also mediates a variety of other physiological and pathological processes. The ubiquitous SNARE machinery and a number of accessory proteins have been implicated in regulating secretion in platelet. Although several platelet SNAREs have been identified, further members of the SNARE family may be needed to fine-tune platelet secretion. In this study we identified expression of the t-SNARE syntaxin 8 (STX8) (Qc SNARE) in mouse and human platelets. In mouse studies, whereas STX8 was not essential for alpha-granule or lysosome secretion, Stx8(-/-) platelets showed a significant defect in dense granule secretion in response to thrombin and CRP. This was most pronounced at intermediate concentrations of agonists. They also showed an aggregation defect that could be rescued with exogenous ADP and increased embolization in Stx8(-/-) mice in vivo consistent with an important autocrine and paracrine role for ADP in aggregation and thrombus stabilization. STX8 therefore specifically contributes to dense granule secretion and represents another member of a growing family of genes that play distinct roles in regulating granule release from platelets and thus platelet function in thrombosis and hemostasis.
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