Abstract Number: OC 10.4
Meeting: ISTH 2022 Congress
Theme: Platelets and Megakaryocytes » Platelet Function and Interactions
Background: Platelets use SNARE-mediated exocytosis to maintain hemostasis and thrombosis via secretion from three types of platelet granules: dense, α, and lysosomal. To understand how SNAREs are regulated, we determined if α-synuclein, a potential v/R-SNARE chaperone, and its binding partner, Cysteine String Protein-α (CSPα), affect platelet secretion and thus hemostasis. These abundant proteins are the only detectible members of their respective families, present in platelets.
Aims: To address the role(s) of α-synuclein and Cysteine String Protein-α in platelets.
Methods: We examined the hemostatic phenotypes of α-synuclein-/- and CSPα-/- mice. Secretion by platelets from these mice was measured using kinetic assays. Platelet aggregation and ADP release were examined with Lumi-aggregometry. Platelet activation was also examined using cytometry. Hemostasis was evaluated in different injury contexts using tail-bleeding, FeCl3 carotid injury, and jugular puncture models. The levels of the platelet secretory machinery were determined by western blotting.
Results: α-Synuclein-/- platelets were defective for dense granule release and less so from lysosomal granule release; however, α granule release was similar to wild-type platelets. Tail-bleeding times for α-synuclein-/- mice were slightly increased compared to wild-type mice, but bleeding from CSPα-/- mice was greatly increased. Occlusion times in the FeCl3 carotid injury model and cessation of bleeding in the jugular puncture model were similar between α-synuclein-/- and wild-type mice. The dominant v/R-SNARE, VAMP-8, was reduced in α-synuclein-/- platelets, while the other v/R-SNARE and t/Q-SNARE levels remained unchanged. Further experiments are underway to determine how α-synuclein and CSPα interact with the secretory machinery to affect hemostasis.
Conclusion(s): These experiments demonstrate a role for α-synuclein and CSPα in platelet exocytosis and hemostasis and will fill gaps in our knowledge of α-synuclein’s physiological function and our understanding of how platelet exocytosis is regulated.
This work is supported by the NIH/NHLBI (HL56652, HL138179, HL150818), VA, and an NSF KY-WV LSAMP BD Fellowship (NSF HRD 2004710).
To cite this abstract in AMA style:
Smith A, Omali L, Joshi S, Whiteheart S. The Role of α-Synuclein and Cysteine String Protein-α in Platelet Function [abstract]. https://abstracts.isth.org/abstract/the-role-of-%ce%b1-synuclein-and-cysteine-string-protein-%ce%b1-in-platelet-function/. Accessed September 21, 2023.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-role-of-%ce%b1-synuclein-and-cysteine-string-protein-%ce%b1-in-platelet-function/