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

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Koester, Anna M. and Geiser, Angéline and Laidlaw, Kamilla M.E. and Morris, Silke and Cutiongco, Marie F.A. and Stirrat, Laura and Gadegaard, Nikolaj and Boles, Eckhard and Black, Hannah L. and Bryant, Nia J. and Gould, Gwyn W. (2022) EFR3 and phosphatidylinositol 4-kinase IIIα regulate insulin-stimulated glucose transport and GLUT4 dispersal in 3T3-L1 adipocytes. Bioscience Reports, 42 (7). pp. 1-13. BSR20221181. ISSN 1573-4935 (https://doi.org/10.1042/BSR20221181)

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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 plasmamembrane 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 plasmamembrane away from the sites of vesicle fusion. EFR3 is a scaffold protein that facilitates localization of phosphatidylinositol 4-kinase type IIIα to the cell surface. Here we show that knockdown of EFR3 or phosphatidylinositol 4-kinase type IIIα 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.

ORCID iDs

Koester, Anna M., Geiser, Angéline ORCID logoORCID: https://orcid.org/0000-0002-7108-2440, Laidlaw, Kamilla M.E., Morris, Silke, Cutiongco, Marie F.A., Stirrat, Laura, Gadegaard, Nikolaj, Boles, Eckhard, Black, Hannah L., Bryant, Nia J. and Gould, Gwyn W. ORCID logoORCID: https://orcid.org/0000-0001-6571-2875;
CORE (COnnecting REpositories)