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PMID: 11502760 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation.

The Journal of cell biology ·Vol. 154 ·No. 4 ·2001-08-20 ·Pages 829-40

Watson RT, Shigematsu S, Chiang SH, Mora S, Kanzaki M, Macara IG, Saltiel AR, Pessin JE

Abstract

Recent studies indicate that insulin stimulation of glucose transporter (GLUT)4 translocation requires at least two distinct insulin receptor-mediated signals: one leading to the activation of phosphatidylinositol 3 (PI-3) kinase and the other to the activation of the small GTP binding protein TC10. We now demonstrate that TC10 is processed through the secretory membrane trafficking system and localizes to caveolin-enriched lipid raft microdomains. Although insulin activated the wild-type TC10 protein and a TC10/H-Ras chimera that were targeted to lipid raft microdomains, it was unable to activate a TC10/K-Ras chimera that was directed to the nonlipid raft domains. Similarly, only the lipid raft-localized TC10/ H-Ras chimera inhibited GLUT4 translocation, whereas the TC10/K-Ras chimera showed no significant inhibitory activity. Furthermore, disruption of lipid raft microdomains by expression of a dominant-interfering caveolin 3 mutant (Cav3/DGV) inhibited the insulin stimulation of GLUT4 translocation and TC10 lipid raft localization and activation without affecting PI-3 kinase signaling. These data demonstrate that the insulin stimulation of GLUT4 translocation in adipocytes requires the spatial separation and distinct compartmentalization of the PI-3 kinase and TC10 signaling pathways.

MeSH Terms
Adipocytes/cytology Amino Acid Sequence Animals Caveolae Caveolin 1 Caveolins/genetics,isolation & purification Cells, Cultured Glucose Transporter Type 4 Insulin/metabolism Membrane Microdomains/metabolism Mice Molecular Sequence Data Monosaccharide Transport Proteins/metabolism Muscle Proteins Mutation Protein Transport Recombinant Fusion Proteins/metabolism Signal Transduction ras Proteins/genetics rho GTP-Binding Proteins/genetics,metabolism
Chemicals
Cav1 protein, mouse Caveolin 1 Caveolins Glucose Transporter Type 4 Insulin Monosaccharide Transport Proteins Muscle Proteins Recombinant Fusion Proteins Slc2a4 protein, mouse Rhoq protein, mouse ras Proteins rho GTP-Binding Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Watson R T
Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
Shigematsu S
Chiang S H
Mora S
Kanzaki M
Macara I G
Saltiel A R
Pessin J E
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200102078
Published
2001-08-20
Epub
2001-00-13
Pages
829-40
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2196453
Subset
IM
Grants
NIDDK NIH HHS · R37 DK033823 · United States
NIDDK NIH HHS · R01 DK033823 · United States
NIDDK NIH HHS · DK49781 · United States
NIDDK NIH HHS · DK25295 · United States
NIDDK NIH HHS · DK33823 · United States
NIDDK NIH HHS · R01 DK049781 · United States
External Links
PubMed source DOI: 10.1083/jcb.200102078 PMC Full Text View journal details
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