The complementary roles of VAMP-2, -3, and -7 in platelet secretion and function

Authors

Smita Joshi, University of KentuckyFollow
Kanakanagavalli Shravani Prakhya, University of KentuckyFollow
Alexis N. Smith, University of Kentucky
Harry Chanzu, University of Kentucky
Ming Zhang, University of Kentucky
Sidney W. Whiteheart, University of KentuckyFollow

Abstract

Platelet secretion requires Soluble N-ethylmaleimide Sensitive Attachment Protein Receptors (SNAREs). Vesicle SNAREs/Vesicle-Associated Membrane Proteins (v-SNAREs/ VAMPs) on granules and t-SNAREs in plasma membranes mediate granule release. Platelet VAMP heterogeneity has complicated the assessment of how/if each is used and affects hemostasis. To address the importance of VAMP-7 (V7), we analyzed mice with global deletions of V3 and V7 together or platelet-specific deletions of V2, V3, and global deletion of V7. We measured the kinetics of cargo release, and its effects on three injury models to define the context-specific roles of these VAMPs. Loss of V7 minimally affected dense and α granule release but did affect lysosomal release. V3−/−7−/− and V2Δ3Δ7−/− platelets showed partial defects in α and lysosomal release; dense granule secretion was unaffected. In vivo assays showed that loss of V2, V3, and V7 caused no bleeding or occlusive thrombosis. These data indicate a role for V7 in lysosome release that is partially compensated by V3. V7 and V3, together, contribute to α granule release, however none of these deletions affected hemostasis/thrombosis. Our results confirm the dominance of V8. When it is present, deletion of V2, V3, or V7 alone or in combination minimally affects platelet secretion and hemostasis.

Document Type

Article

Publication Date

2023

Notes/Citation Information

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

Digital Object Identifier (DOI)

https://doi.org/10.1080/09537104.2023.2237114

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.

Repository Citation

Joshi, Smita; Prakhya, Kanakanagavalli Shravani; Smith, Alexis N.; Chanzu, Harry; Zhang, Ming; and Whiteheart, Sidney W., "The complementary roles of VAMP-2, -3, and -7 in platelet secretion and function" (2023). Saha Cardiovascular Research Center Faculty Publications. 69.
https://uknowledge.uky.edu/cvrc_facpub/69