α-Synuclein is the major platelet isoform but is dispensable for activation, secretion, and thrombosis

• Published in: Platelets (Edinburgh) 2023-12, Vol.34 (1), p.2267147-2267147
• Main Authors: Smith, Alexis N, Joshi, Smita, Chanzu, Harry, Alfar, Hammodah R, Shravani Prakhya, Kanakanagavalli, Whiteheart, Sidney W
• Format: Article
• Language: English
• Subjects: alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Animals; Blood Platelets - metabolism; Cytoplasmic Granules - metabolism; Exocytosis; Exocytosis - physiology; hemostasis; Mice; Mice, Knockout; Platelet Activation; platelets; Protein Isoforms - metabolism; SNARE Proteins - metabolism; Thrombosis - metabolism; VAMP; α-synuclein
• ISSN: 0953-7104; 1369-1635; 1369-1635
• DOI: 10.1080/09537104.2023.2267147

Platelets play many roles in the vasculature ensuring proper hemostasis and maintaining integrity. These roles are facilitated, in part, by cargo molecules released from platelet granules via oluble SF ttachment rotein eceptor (SNARE) mediated membrane fusion, which is controlled by several protein-protein interactions. Chaperones have been characterized for t-SNAREs ( . Munc18b for Syntaxin-11), but none have been clearly identified for v-SNAREs. α-Synuclein has been proposed as a v-SNARE chaperone which may affect SNARE-complex assembly, fusion pore opening, and thus secretion. Despite its abundance and that it is the only isoform present, α-synuclein's role in platelet secretion is uncharacterized. In this study, immunofluorescence showed that α-synuclein was present on punctate structures that co-stained with markers for α-granules and lysosomes and in a cytoplasmic pool. We analyzed the phenotype of α-synuclein mice and their platelets. Platelets from knockout mice had a mild, agonist-dependent secretion defect but aggregation and spreading were unaffected. Consistently, thrombosis/hemostasis were unaffected in the tail-bleeding, FeCl carotid injury and jugular vein puncture models. None of the platelet secretory machinery examined, . the v-SNAREs, were affected by α-synuclein's loss. The results indicate that, despite its abundance, α-synuclein has only a limited role in platelet function and thrombosis.