EFR3 and phosphatidylinositol 4-kinase IIIα regulate insulin-stimulated glucose transport and GLUT4 dispersal in 3T3-L1 adipocytes

Koester, A. M. et al. (2022) EFR3 and phosphatidylinositol 4-kinase IIIα regulate insulin-stimulated glucose transport and GLUT4 dispersal in 3T3-L1 adipocytes. Bioscience Reports, 42(7), BSR20221181. (doi: 10.1042/BSR20221181) (PMID:35735144) (PMCID:PMC9272592)

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Abstract

Insulin stimulates glucose transport in muscle and adipocytes. This is achieved by regulated delivery of intracellular glucose transporter (GLUT4)-containing vesicles to the plasma membrane where they dock and fuse, resulting in increased cell surface GLUT4 levels. Recent work identified a potential further regulatory step, in which insulin increases the dispersal of GLUT4 in the plasma membrane away from the sites of vesicle fusion. EFR3 is a scaffold protein that facilitates localisation of phosphatidylinositol 4-kinase type IIIa to the cell surface. Here we show that knockdown of EFR3 or phosphatidylinositol 4-kinase type IIIa impairs insulin-stimulated glucose transport in adipocytes. Using direct stochastic reconstruction microscopy, we also show that EFR3 knockdown impairs insulin stimulated GLUT4 dispersal in the plasma membrane. We propose that EFR3 plays a previously unidentified role in controlling insulin-stimulated glucose transport by facilitating dispersal of GLUT4 within the plasma membrane.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Koester, Anna and Gould, Professor Gwyn and Black, Hannah Lucy and Cutiongco, Ms Marie and LAIDLAW, Kamilla and Bryant, Dr Nia and Gadegaard, Professor Nikolaj and Stirrat, Mrs Laura and Morris, Silke
Authors: Koester, A. M., Geiser, A., Laidlaw, K. M.E., Morris, S., Cutiongco, M. F.A., Stirrat, L., Gadegaard, N., Boles, E., Black, H. L., Bryant, N., and Gould, G. W.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Bioscience Reports
Publisher:Portland Press
ISSN:0144-8463
ISSN (Online):1573-4935
Published Online:23 June 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Bioscience Reports 42(7): BSR20221181
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190812BHF 4 Year PhD Studentship AwardRhian TouyzBritish Heart Foundation (BHF)FS/14/61/31284Institute of Cardiovascular & Medical Sciences
173377How does Cholesterol regulate insulin action in adipocytes?Gwyn GouldDiabetes UK (DIABETUK)15/0005246Institute of Molecular, Cell & Systems Biology
169439Investigation of EFR3's role in regulating phosphatidyl-inositol-4-phosphate patches in the plasma membrane of adipocytes to mediate insulin-dependent dispersal of GLUT4 clustersGwyn GouldDiabetes UK (DIABETUK)13/0004696Institute of Molecular, Cell & Systems Biology
172025FAKIR: Focal Adhesion Kinetics In nanosurface RecognitionNikolaj GadegaardEuropean Research Council (ERC)648892ENG - Biomedical Engineering