Increased activity of the Vesicular Soluble N -Ethylmaleimide-sensitive Factor Attachment Protein Receptor TI-VAMP/VAMP7 by Tyrosine Phosphorylation in the Longin Domain

Abstract : Vesicular (v)- and target (t)-SNAREs play essential roles in intracellular membrane fusion through the formation of cytoplasmic α-helical bundles. Several v-SNAREs have a Longin N-terminal extension that, by promoting a closed conformation, plays an autoinhibitory function and decreases SNARE complex formation and membrane fusion efficiency. The molecular mechanism leading to Longin v-SNARE activation is largely unknown. Here we find that exocytosis mediated by the Longin v-SNARE TI-VAMP/VAMP7 is activated by tonic treatment with insulin and insulin-like growth factor-1 but not by depolarization and intracellular calcium rise. In search of a potential downstream mechanism, we found that TI-VAMP is phosphorylated in vitro by c-Src kinase on tyrosine 45 of the Longin domain. Accordingly, a mutation of tyrosine 45 into glutamate, but not phenylalanine, activates both t-SNARE binding and exocytosis. Activation of TI-VAMP-mediated exocytosis thus relies on tyrosine phosphorylation.
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https://hal-univ-evry.archives-ouvertes.fr/hal-02177558
Contributor : Andrea Burgo <>
Submitted on : Tuesday, July 9, 2019 - 10:43:23 AM
Last modification on : Thursday, July 11, 2019 - 1:19:51 AM

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Andrea Burgo, Alessandra Casano, Aurelia Kuster, Stefan Arold, Guan Wang, et al.. Increased activity of the Vesicular Soluble N -Ethylmaleimide-sensitive Factor Attachment Protein Receptor TI-VAMP/VAMP7 by Tyrosine Phosphorylation in the Longin Domain. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2013, 288 (17), pp.11960-11972. ⟨10.1074/jbc.M112.415075⟩. ⟨hal-02177558⟩

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