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PMID: 12134080 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

GLUT4 retention in adipocytes requires two intracellular insulin-regulated transport steps.

Molecular biology of the cell ·Vol. 13 ·No. 7 ·2002-07-00 ·Pages 2421-35

Zeigerer A, Lampson MA, Karylowski O, Sabatini DD, Adesnik M, Ren M, McGraw TE

Abstract

Insulin regulates glucose uptake into fat and muscle by modulating the distribution of the GLUT4 glucose transporter between the surface and interior of cells. The GLUT4 trafficking pathway overlaps with the general endocytic recycling pathway, but the degree and functional significance of the overlap are not known. In this study of intact adipocytes, we demonstrate, by using a compartment-specific fluorescence-quenching assay, that GLUT4 is equally distributed between two intracellular pools: the transferrin receptor-containing endosomes and a specialized compartment that excludes the transferrin receptor. These pools of GLUT4 are in dynamic communication with one another and with the cell surface. Insulin-induced redistribution of GLUT4 to the surface requires mobilization of both pools. These data establish a role for the general endosomal system in the specialized, insulin-regulated trafficking of GLUT4. Trafficking through the general endosomal system is regulated by rab11. Herein, we show that rab11 is required for the transport of GLUT4 from endosomes to the specialized compartment and for the insulin-induced translocation to the cell surface, emphasizing the importance of the general endosomal pathway in the specialized trafficking of GLUT4. Based on these findings we propose a two-step model for GLUT4 trafficking in which the general endosomal recycling compartment plays a specialized role in the insulin-regulated traffic of GLUT4. This compartment-based model provides the framework for understanding insulin-regulated trafficking at a molecular level.

MeSH Terms
3T3 Cells Adipocytes/cytology,metabolism Animals Biological Transport/physiology Cytoplasmic Vesicles/metabolism Endosomes/metabolism Fluorescent Dyes/metabolism Glucose/metabolism Glucose Transporter Type 4 Humans Insulin/metabolism Mice Monosaccharide Transport Proteins/genetics,metabolism Muscle Proteins Receptors, Transferrin/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Transferrin/metabolism rab GTP-Binding Proteins/metabolism
Chemicals
Fluorescent Dyes Glucose Transporter Type 4 Insulin Monosaccharide Transport Proteins Muscle Proteins Receptors, Transferrin Recombinant Fusion Proteins SLC2A4 protein, human Slc2a4 protein, mouse Transferrin rab11 protein rab GTP-Binding Proteins Glucose
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Zeigerer Anja
Department of Biochemistry, Biophysics and Molecular Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
Lampson Michael A
Karylowski Ola
Sabatini David D
Adesnik Milton
Ren Mindong
McGraw Timothy E
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e02-02-0071
Published
2002-07-00
Pages
2421-35
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC117324
Subset
IM
Grants
NIDDK NIH HHS · R01 DK052852 · United States
NIDDK NIH HHS · R01 DK057689 · United States
NIDDK NIH HHS · DK-52852 · United States
NIDDK NIH HHS · DK-57689 · United States
External Links
PubMed source DOI: 10.1091/mbc.e02-02-0071 PMC Full Text View journal details
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