Endobrevin/VAMP-8 Is the Primary v-SNARE for the Platelet Release Reaction

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

doi:10.1091/mbc.e06-09-0785

Cited by 143 publications

(204 citation statements)

References 48 publications

(68 reference statements)

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“…In 2010, Kondkar et al [26] reported that increased levels of vesicle-associated membrane protein 8 (VAMP8)/endobrevin mRNA were associated with platelet hyperreactivity, and that miR-96 could regulate VAMP8/endobrevin mRNA levels in cultured cells. The authors concluded that these data support a role for VAMP8/endobrevin in the heterogeneity of platelet reactivity, and suggest a role for miR-96 in regulating expression of VAMP8, the primary platelet v-SNARE protein involved in the platelet secretion process [27].…”

Section: A Role For Micrornas In Platelet Function?mentioning

confidence: 89%

The clinical significance of platelet microparticle-associated microRNAs

Provost

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Abstract:Circulating blood platelets play a central role in the maintenance of hemostasis. They adhere to subendothelial extracellular matrix proteins that become exposed upon vessel wall damage, which is followed by platelet activation, further platelet recruitment, platelet aggregation and formation of an occlusive, or non-occlusive, platelet thrombus. Platelets host a surprisingly diverse transcriptome, which is comprised of ~ 9500 messenger RNAs (mRNAs) and different classes of non-coding RNAs, including microRNAs, as well as a significant repertoire of proteins that contribute to their primary (adhesion, aggregation, granule secretion) and alternative (RNA transfer, mRNA translation, immune regulation) functions. Platelets have the propensity to release microparticles (MPs; 0.1-1 μm in diameter) upon activation, which may mediate inflammatory responses and contribute to exacerbate inflammatory diseases and conditions. Carrying components of the platelets' cytoplasm, platelet MPs may exert their effects on recipient cells by transferring their content in platelet-derived bioactive lipid mediators, cytokines, mRNAs and microRNAs. Platelet MP-associated microRNAs may thus function also outside of platelets and play an important role in intercellular signaling and gene expression programming across the entire circulatory system. The role and importance of platelet MP-associated microRNAs in various aspects of biology and pathophysiology are increasingly recognized, and now provide the scientific basis and rationale to support further translational research and clinical studies. The clinical significance, pathophysiological role as well as the diagnostic and therapeutic potential of platelet MP-associated microRNAs in cardiovascular diseases, platelet transfusion and cancer will be discussed.

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Section: A Role For Micrornas In Platelet Function?mentioning

confidence: 89%

The clinical significance of platelet microparticle-associated microRNAs

Provost

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…VAMP8 encodes vesicle-associated membrane protein 8, a member of the SNARE complex, that mediates membranemembrane fusion and platelet degranulation. 26,27 SNX19 encodes sorting nexin 19, a member of the nexin family that is involved in intracellular trafficking of membrane vesicles. 28 The sorting nexin 19 protein product has been shown to interact with islet antigen-2, a transmembrane protein tyrosine phosphatase associated with dense core secretory vesicles and a major autoantigen in type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Five common gene variants identify elevated genetic risk for coronary heart disease

Bare¹,

Morrison

Rowland³

et al. 2007

Genetics in Medicine

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Purpose: Because multiple genetic variants influence risk for coronary heart disease, we combined multiple variants that had been associated with coronary heart disease in several studies into a genetic risk score and asked whether a high genetic risk score would be significantly associated with coronary heart disease after accounting for traditional risk factors. Methods: We considered five variants that were associated with coronary heart disease in two studies and confirmed in the Atherosclerosis Risk in Communities study: rs20455 (KIF6), rs3900940 (MYH15), rs7439293 (PALLD), rs2298566 (SNX19), and rs1010 (VAMP8). We calculated a genetic risk score for each Atherosclerosis Risk in Communities study participant and estimated the hazard ratio for incident coronary heart disease of a high genetic risk score (compared with not-high) in Cox models that adjusted for traditional risk factors during a median of 13 years of follow-up. Results: For white participants with a high genetic risk score (4% of the 9129 whites), compared with those without a high genetic risk score, the hazard ratio for incident coronary heart disease was 1.57 (95% confidence interval 1.21-2.04; P ϭ 0.001). Internal validation using bootstrap samples estimated that a hazard ratio of 1.43 could be expected in external populations. Conclusions:After adjusting for traditional risk factors, those with a high genetic risk score had a 57% increased risk of incident coronary heart disease in the Atherosclerosis Risk in Communities study. Genet Med 2007:9(10):682-689.

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“…Subsequently it has been shown that VAMP8 is involved in exocytosis in pancreatic acinar cells (16), mast cells (17,18), cytotoxic T lymphocytes (19), platelets (20,21), and kidney collecting duct epithelia (22).…”

mentioning

confidence: 99%

Vesicle-associated Membrane Protein 8 (VAMP8) Is a SNARE (Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor) Selectively Required for Sequential Granule-to-granule Fusion

Behrendorff

Dolai

Hong

et al. 2011

Journal of Biological Chemistry

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Compound exocytosis is found in many cell types and is the major form of regulated secretion in acinar and mast cells. Its key characteristic is the homotypic fusion of secretory granules. These then secrete their combined output through a single fusion pore to the outside. The control of compound exocytosis remains poorly understood. Although soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) such as syntaxin 2, SNAP23 (synaptosome-associated protein of 23 kDa), and SNAP25 have been suggested to play a role, none has been proven. Vesicle-associated membrane protein 8 (VAMP8) is a SNARE first associated with endocytic processes but more recently has been suggested as an R-SNARE in regulated exocytosis. Secretion in acinar cells is reduced when VAMP8 function is inhibited and is less in VAMP8 knock-out mice. Based on electron microscopy experiments, it was suggested that VAMP8 may be involved in compound exocytosis. Here we have tested the hypothesis that VAMP8 controls homotypic granule-to-granule fusion during sequential compound exocytosis. We use a new assay to distinguish primary fusion events (fusion with the cell membrane) from secondary fusion events (granule-granule fusion). Our data show the pancreatic acinar cells from VAMP8 knock-out animals have a specific reduction in secondary granule fusion but that primary granule fusion is unaffected. Furthermore, immunoprecipitation experiments show syntaxin 2 association with VAMP2, whereas syntaxin 3 associates with VAMP8. Taken together our data indicate that granule-to-granule fusion is regulated by VAMP8 containing SNARE complexes distinct from those that regulate primary granule fusion.The precise role of compound exocytosis has not been determined, but it is thought that it might enhance secretion by enabling fusion of, and release of contents from, granules that lie deeper within the cell (1). For example, in the case of the massive exocytosis observed during mast cell degranulation (2), compound exocytosis would ensure that secretion occurs both through fusion of granules close to the plasma membrane and from deeper lying granules. This avoids the need to transport deeper granules up to the cell membrane and so would accelerate the secretory response.In the case of acinar cells the apical plasma membrane area is relatively small compared with the total membrane area and is defined by tight junctional boundaries (3). Regulated exocytosis occurs exclusively at the apical membrane. Secretory (zymogen) granules are tightly packed in the apical region of acinar cells (see Fig. 1) and do not move over the minute timescales we use for stimulation. This means that only a few granules have direct access to the apical plasma membrane. Furthermore, granule fusion is so slow (many minutes) that close granules would limit access of deeper-lying granules to docking sites at the plasma membrane. Compound exocytosis provides a mechanism to enhance secretion by enabling deeper granules to fuse with peripheral granules and so release their c...

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Endobrevin/VAMP-8 Is the Primary v-SNARE for the Platelet Release Reaction

Cited by 143 publications

References 48 publications

The clinical significance of platelet microparticle-associated microRNAs

The clinical significance of platelet microparticle-associated microRNAs

Five common gene variants identify elevated genetic risk for coronary heart disease

Vesicle-associated Membrane Protein 8 (VAMP8) Is a SNARE (Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor) Selectively Required for Sequential Granule-to-granule Fusion

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