title: Identification of roles for the SNARE-associated protein, SNAP29, in mouse platelets.
abstract: Platelets are critical for maintaining vascular hemostasis, but also play a major role in the formation of occlusive cardiovascular and cerebrovascular thrombi under disease conditions. Secretion of platelet alpha and dense granules is a requirement for efficient thrombus formation. Understanding and targeting the mechanisms of secretion is important to aid the development of effective antithrombotics. SNAP29 is a tSNARE found in platelets, but whose role has not been defined. Using a platelet-specific SNAP29 knockout mouse model, we assessed the role of SNAP29 in platelet secretion and function under standardized conditions and also in in vitro and in vivo thrombosis. The data showed no major defects in SNAP29-null platelets, but revealed a minor defect in α-granule secretion and a significant increase in embolization rate of thrombi in vivo. These data suggest that SNAP29 contributes to the regulation of platelet α-granule secretion and thrombus stability, possibly partially masked by functional redundancy with other tSNAREs, such as SNAP23.
authors.affiliation: a School of Physiology & Pharmacology , University of Bristol , Bristol , UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Williams
authors.affiliation: a School of Physiology & Pharmacology , University of Bristol , Bristol , UK.|b Cancer Research UK Clinical Trials Unit (CRCTU), School of Cancer Sciences , University of Birmingham , Edgbaston, Birmingham , UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Savage
authors.affiliation: a School of Physiology & Pharmacology , University of Bristol , Bristol , UK.|c Department of Pharmacology , University of Cambridge , Cambridge , UK.
authors.forename: M T
authors.initials: MT
authors.lastname: Harper
authors.affiliation: a School of Physiology & Pharmacology , University of Bristol , Bristol , UK.
authors.forename: S F
authors.initials: SF
authors.lastname: Moore
authors.affiliation: a School of Physiology & Pharmacology , University of Bristol , Bristol , UK.
authors.forename: I
authors.initials: I
authors.lastname: Hers
authors.affiliation: a School of Physiology & Pharmacology , University of Bristol , Bristol , UK.
authors.forename: A W
authors.initials: AW
authors.lastname: Poole
mesh_terms: D000818:Animals; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D023061:Gene Order; D056426:Genetic Loci; D051379:Mice; D018345:Mice, Knockout; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011485:Protein Binding; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050767:Qc-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D010980:Platelet Membrane Glycoproteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D050600:SNARE Proteins; C486621:Snap29 protein, mouse
keywords: Gene knockout; Snap29 protein; mouse; platelets; secretion; thrombosis