Munc18c phosphorylation by the insulin receptor links cell signaling directly to SNARE exocytosis
ORCID
Latha Ramalingam: 0000-0002-4856-7327
Document Type
Article
Date
4-2011
Disciplines
Nutrition
Description/Abstract
How the Sec1/Munc18-syntaxin complex might transition to form the SNARE core complex remains unclear. Toward this, Munc18c tyrosine phosphorylation has been correlated with its dissociation from syntaxin 4. Using 3T3-L1 adipocytes subjected to small interfering ribonucleic acid reduction of Munc18c as a model of impaired insulin-stimulated GLUT4 vesicle exocytosis, we found that coordinate expression of Munc18c-wild type or select phosphomimetic Munc18c mutants, but not phosphodefective mutants, restored GLUT4 vesicle exocytosis, suggesting a requirement for Munc18c tyrosine phosphorylation at Tyr219 and Tyr521. Surprisingly, the insulin receptor (IR) tyrosine kinase was found to target Munc18c at Tyr521 in vitro, rapidly binding and phosphorylating endogenous Munc18c within adipocytes and skeletal muscle. IR, but not phosphatidylinositol 3-kinase, activation was required. Altogether, we identify IR as the first known tyrosine kinase for Munc18c as part of a new insulin-signaling step in GLUT4 vesicle exocytosis, exemplifying a new model for the coordination of SNARE assembly and vesicle mobilization events in response to a single extracellular stimulus.
Recommended Citation
Jewell JL, Oh E, Ramalingam L, Kalwat MA, Tagliabracci VS, Tackett L, Elmendorf JS, Thurmond DC. Munc18c phosphorylation by the insulin receptor links cell signaling directly to SNARE exocytosis. J Cell Biol. 2011 Apr 4;193(1):185-99. doi: 10.1083/jcb.201007176. Epub 2011 Mar 28. PMID: 21444687; PMCID: PMC3082181.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
