Syntaxin 11 regulates platelet granule release and hemostasis

Abstract

Degranulation, a form of regulated exocytosis, is essential for platelet participation in hemostasis. The interaction between Syntaxin (Stx) and Munc18 proteins is required for exocytosis. We have proven that selective genetic deletion of Munc18-2 eliminates regulated exocytosis in platelets, but its Stx partner was not known. Among the exocytic Stx (1A, 1B, 2, 3, 4, and 11), we proved that Stxs1A, 1B, and 3 are not expressed platelets. Others have shown that deletion of Stx2 and 4 had no consequences on platelet degranulation. Now our goal is to study if Stx11 is involved in platelet exocytosis. We created a Stx11 conditional knockout mouse and crossed it with a platelet-specific Cre mouse to generate cell-specific Stx11 deletants. We evaluated the exocytosis of individual subpopulations of platelet granules stimulated with thrombin or collagen. Platelets lacking Stx11 had a marked decrease in dense granule exocytosis with both agonists, but alpha and lysosomal granules were only affected when thrombin was used. Stx11-deficient platelets had no deficiency in granule biogenesis and were capable of undergoing full activation. Platelets from Stx11 deletant mice had deficient aggregation and ex vivo thrombus formation. In vivo, all these defects translated into protection from arterial thrombosis, and in abnormal hemostasis after venous and arterial injury, in mice lacking Stx11 in their platelets.