Tyrosine phosphorylation of Munc18c on residue 521 abrogates binding to Syntaxin 4

Aran, V., Bryant, N.J. and Gould, G.W. (2011) Tyrosine phosphorylation of Munc18c on residue 521 abrogates binding to Syntaxin 4. BMC Biochemistry, 12(19), (doi:10.1186/1471-2091-12-19)

[img]
Preview
Text
ID52842.pdf
Available under License Creative Commons Attribution.

2MB

Publisher's URL: http://dx.doi.org/10.1186/1471-2091-12-19

Abstract

Background: Insulin stimulates exocytosis of GLUT4 from an intracellular store to the cell surface of fat and muscle cells. Fusion of GLUT4-containing vesicles with the plasma membrane requires the SNARE proteins Syntaxin 4, VAMP2 and the regulatory Sec1/Munc18 protein, Munc18c. Syntaxin 4 and Munc18c form a complex that is disrupted upon insulin treatment of adipocytes. Munc18c is tyrosine phosphorylated in response to insulin in these cells. Here, we directly test the hypothesis that tyrosine phosphorylation of Munc18c is responsible for the observed insulin-dependent abrogation of binding between Munc18c and Syntaxin 4. Results: We show that Munc18c is directly phosphorylated by recombinant insulin receptor tyrosine kinase in vitro. Using pull-down assays, we show that phosphorylation abrogates binding of Munc18c to both Syntaxin 4 and the v-SNARE VAMP2, as does the introduction of a phosphomimetic mutation into Munc18c ( Y521E). Conclusion: Our data indicate that insulin-stimulated tyrosine phosphorylation of Munc18c impairs the ability of Munc18c to bind its cognate SNARE proteins, and may therefore represent a regulatory step in GLUT4 traffic.

Item Type:Articles
Additional Information:This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gould, Professor Gwyn and Bryant, Dr Nia
Authors: Aran, V., Bryant, N.J., and Gould, G.W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:BMC Biochemistry
Publisher:BioMed Central Ltd.
ISSN (Online):1471-2091
Published Online:06 May 2011
Copyright Holders:Copyright © 2011 Aran et al; licensee BioMed Central Ltd.
First Published:First published in BMC Biochemistry 12 (19)
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record