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

Alexis N. Smith, Smita Joshi, Harry Chanzu, Hammodah R. Alfar, Kanakanagavalli Shravani Prakhya, Sidney W. Whiteheart

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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. 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 in vitro were unaffected. Consistently, thrombosis/hemostasis were unaffected in the tail-bleeding, FeCl3 carotid injury and jugular vein puncture models. None of the platelet secretory machinery examined, e.g. 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.

Original languageEnglish
Article number2267147
JournalPlatelets
Volume34
Issue number1
DOIs
StatePublished - 2023

Bibliographical note

Funding Information:
The work was supported by grants from the NIH, NHLBI [HL56652, HL138179, and HL150818], and a Department of Veterans Affairs Merit Award to S.W.W., and an NSF KY-WV LSAMP BD Fellowship [NSF HRD 2004710] awarded to A.N.S. The authors thank Dr. Jeremy P. Wood and the members of the Whiteheart Laboratory for their careful perusal of this manuscript and their patience. They are thankful for the efforts of Ming Zhang in managing the mouse colony.

Publisher Copyright:
© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.

Keywords

  • Exocytosis
  • VAMP
  • hemostasis
  • platelets
  • α-synuclein

ASJC Scopus subject areas

  • Hematology

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