| First Author | Smith AN | Year | 2023 |
| Journal | Platelets | Volume | 34 |
| Issue | 1 | Pages | 2267147 |
| PubMed ID | 37927048 | Mgi Jnum | J:358288 |
| Mgi Id | MGI:7778527 | Doi | 10.1080/09537104.2023.2267147 |
| Citation | Smith AN, et al. (2023) alpha-Synuclein is the major platelet isoform but is dispensable for activation, secretion, and thrombosis. Platelets 34(1):2267147 |
| abstractText | 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 Soluble NSF Attachment Protein Receptor (SNARE) mediated membrane fusion, which is controlled by several protein-protein interactions. Chaperones have been characterized for t-SNAREs (i.e. Munc18b for Syntaxin-11), but none have been clearly identified for v-SNAREs. alpha-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, alpha-synuclein's role in platelet secretion is uncharacterized. In this study, immunofluorescence showed that alpha-synuclein was present on punctate structures that co-stained with markers for alpha-granules and lysosomes and in a cytoplasmic pool. We analyzed the phenotype of alpha-synuclein(-/-) mice and their platelets. Platelets from knockout mice had a mild, agonist-dependent secretion defect but aggregation and spreading in vitro were unaffected. Consistently, thrombosis/hemostasis were unaffected in the tail-bleeding, FeCl(3) carotid injury and jugular vein puncture models. None of the platelet secretory machinery examined, e.g. the v-SNAREs, were affected by alpha-synuclein's loss. The results indicate that, despite its abundance, alpha-synuclein has only a limited role in platelet function and thrombosis. |
