Endobrevin/VAMP-8 is the primary v-SNARE for the platelet release reaction

Qiansheng Ren, Holly Kalani Barber, Garland L. Crawford, Zubair A. Karim, Chunxia Zhao, Wangsun Choi, Cheng Chun Wang, Wanjin Hong, Sidney W. Whiteheart

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

Platelet secretion is critical to hemostasis. Release of granular cargo is mediated by soluble NSF attachment protein receptors (SNAREs), but despite consensus on t-SNAREs usage, it is unclear which Vesicle Associated Membrane Protein (VAMPs: synaptobrevin/VAMP-2, cellubrevin/VAMP-3, TI-VAMP/VAMP-7, and endobrevin/VAMP-8) is required. We demonstrate that VAMP-8 is required for release from dense core granules, alpha granules, and lysosomes. Platelets from VAMP-8-/- mice have a significant defect in agonist-induced secretion, though signaling, morphology, and cargo levels appear normal. In contrast, VAMP-2+/-, VAMP-3-/-, and VAMP-2 +/-/VAMP-3-/- platelets showed no defect. Consistently, tetanus toxin had no effect on secretion from permeabilized mouse VAMP-3 -/- platelets or human platelets, despite cleavage of VAMP-2 and/or -3. Tetanus toxin does block the residual release from permeabilized VAMP-8 -/- platelets, suggesting a secondary role for VAMP-2 and/or -3. These data imply a ranked redundancy of v-SNARE usage in platelets and suggest that VAMP-8-/- mice will be a useful in vivo model to study platelet exocytosis in hemostasis and vascular inflammation.

Original languageEnglish
Pages (from-to)24-33
Number of pages10
JournalMolecular Biology of the Cell
Volume18
Issue number1
DOIs
StatePublished - Jan 2007

Bibliographical note

Funding Information:
The early part of this study was funded by the New Zealand Foundation for Research, Science and Technology under Contract No. CO5X0209 ofthe Institute ofGeological and Nuclear Sciences. The author thanks Jim Cousins, Michelle Salmon, Martha Savage, and three anonymous reviewers. Thanks are also due to helpful and supportive advice on some aspects of the paper from Donna Eberhart-Phillips.

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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