Tyrosine Phosphorylation of Munc18c on Residue 521 Abrogates Binding to Syntaxin 4

Overview

Journal BMC Biochem

Publisher Biomed Central

Specialty Biochemistry

Date 2011 May 10

PMID 21548926

Citations 18

Authors

Veronica Aran

Nia J Bryant

Gwyn W Gould

Affiliations

Soon will be listed here.

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.

Citing Articles

Phosphorylation of Syntaxin 4 by the Insulin Receptor Drives Exocytic SNARE Complex Formation to Deliver GLUT4 to the Cell Surface.

Kioumourtzoglou D, Black H, Al Tobi M, Livingstone R, Petrie J, Boyle J Biomolecules. 2023; 13(12).

PMID: 38136609 PMC: 10741561. DOI: 10.3390/biom13121738.

Phosphorylation of the N-terminus of Syntaxin-16 controls interaction with mVps45 and GLUT4 trafficking in adipocytes.

Bremner S, Berends R, Kaupisch A, Roccisana J, Sutherland C, Bryant N PeerJ. 2023; 11:e15630.

PMID: 37520260 PMC: 10373645. DOI: 10.7717/peerj.15630.

Exocytosis Proteins: Typical and Atypical Mechanisms of Action in Skeletal Muscle.

Hwang J, Thurmond D Front Endocrinol (Lausanne). 2022; 13:915509.

PMID: 35774142 PMC: 9238359. DOI: 10.3389/fendo.2022.915509.

GLUT4 On the move.

Fazakerley D, Koumanov F, Holman G Biochem J. 2022; 479(3):445-462.

PMID: 35147164 PMC: 8883492. DOI: 10.1042/BCJ20210073.

Structure, function and regulation of mammalian glucose transporters of the SLC2 family.

Holman G Pflugers Arch. 2020; 472(9):1155-1175.

PMID: 32591905 PMC: 7462842. DOI: 10.1007/s00424-020-02411-3.

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