TY - JOUR
T1 - Endobrevin/VAMP-8 is the primary v-SNARE for the platelet release reaction
AU - Ren, Qiansheng
AU - Barber, Holly Kalani
AU - Crawford, Garland L.
AU - Karim, Zubair A.
AU - Zhao, Chunxia
AU - Choi, Wangsun
AU - Wang, Cheng Chun
AU - Hong, Wanjin
AU - Whiteheart, Sidney W.
N1 - 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.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
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U2 - 10.1091/mbc.E06-09-0785
DO - 10.1091/mbc.E06-09-0785
M3 - Article
C2 - 17065550
AN - SCOPUS:33846045579
SN - 1059-1524
VL - 18
SP - 24
EP - 33
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 1
ER -