Sorting of GLUT4 into its insulin-sensitive store requires the Sec1/Munc18 protein mVps45

Roccisana, J., Sadler, J.B.A., Bryant, N.J. and Gould, G.W. (2013) Sorting of GLUT4 into its insulin-sensitive store requires the Sec1/Munc18 protein mVps45. Molecular Biology of the Cell, 24(15), pp. 2389-97. (doi:10.1091/mbc.E13-01-0011)

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Abstract

Insulin stimulates glucose transport in fat and muscle cells by regulating delivery of the facilitative glucose transporter, glucose transporter isoform 4 (GLUT4), to the plasma membrane. In the absence of insulin, GLUT4 is sequestered away from the general recycling endosomal pathway into specialized vesicles, referred to as GLUT4-storage vesicles. Understanding the sorting of GLUT4 into this store is a major challenge. Here we examine the role of the Sec1/Munc18 protein mVps45 in GLUT4 trafficking. We show that mVps45 is up-regulated upon differentiation of 3T3-L1 fibroblasts into adipocytes and is expressed at stoichiometric levels with its cognate target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor, syntaxin 16. Depletion of mVps45 in 3T3-L1 adipocytes results in decreased GLUT4 levels and impaired insulin-stimulated glucose transport. Using sub-cellular fractionation and an in vitro assay for GLUT4-storage vesicle formation, we show that mVps45 is required to correctly traffic GLUT4 into this compartment. Collectively our data reveal a crucial role for mVps45 in the delivery of GLUT4 into its specialized, insulin-regulated compartment.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gould, Professor Gwyn and Roccisana, Dr Jennifer and Bryant, Dr Nia
Authors: Roccisana, J., Sadler, J.B.A., 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:Molecular Biology of the Cell
Journal Abbr.:MBoC
ISSN:1059-1524
ISSN (Online):1939-4586

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