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Insulin-promoted mobilization of GLUT4 from a perinuclear storage site requires RAB10.

Citation
Brumfield, A., et al. “Insulin-Promoted Mobilization Of Glut4 From A Perinuclear Storage Site Requires Rab10.”. Molecular Biology Of The Cell, pp. 57-73.
Center Albert Einstein College of Medicine
Author Alexandria Brumfield, Natasha Chaudhary, Dorothee Molle, Jennifer Wen, Johannes Graumann, Timothy E McGraw
Abstract

Insulin controls glucose uptake into muscle and fat cells by inducing a net redistribution of glucose transporter 4 (GLUT4) from intracellular storage to the plasma membrane (PM). The TBC1D4-RAB10 signaling module is required for insulin-stimulated GLUT4 translocation to the PM, although where it intersects GLUT4 traffic was unknown. Here we demonstrate that TBC1D4-RAB10 functions to control GLUT4 mobilization from a -Golgi network (TGN) storage compartment, establishing that insulin, in addition to regulating the PM proximal effects of GLUT4-containing vesicles docking to and fusion with the PM, also directly regulates the behavior of GLUT4 deeper within the cell. We also show that GLUT4 is retained in an element/domain of the TGN from which newly synthesized lysosomal proteins are targeted to the late endosomes and the ATP7A copper transporter is translocated to the PM by elevated copper. Insulin does not mobilize ATP7A nor does copper mobilize GLUT4, and RAB10 is not required for copper-elicited ATP7A mobilization. Consequently, GLUT4 intracellular sequestration and mobilization by insulin is achieved, in part, through utilizing a region of the TGN devoted to specialized cargo transport in general rather than being specific for GLUT4. Our results define the GLUT4-containing region of the TGN as a sorting and storage site from which different cargo are mobilized by distinct signals through unique molecular machinery.

Year of Publication
2021
Journal
Molecular biology of the cell
Volume
32
Issue
1
Number of Pages
57-73
Date Published
12/2021
ISSN Number
1939-4586
DOI
10.1091/mbc.E20-06-0356
Alternate Journal
Mol Biol Cell
PMID
33175605
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