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PMID: 17189207 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Gapex-5, a Rab31 guanine nucleotide exchange factor that regulates Glut4 trafficking in adipocytes.

Cell metabolism ·Vol. 5 ·No. 1 ·2007-01-00 ·Pages 59-72

Lodhi IJ, Chiang SH, Chang L, Vollenweider D, Watson RT, Inoue M, Pessin JE, Saltiel AR

Abstract

Insulin stimulates glucose uptake by promoting translocation of the Glut4 glucose transporter from intracellular storage compartments to the plasma membrane. In the absence of insulin, Glut4 is retained intracellularly; the mechanism underlying this process remains uncertain. Using the TC10-interacting protein CIP4 as bait in a yeast two-hybrid screen, we cloned a RasGAP and VPS9 domain-containing protein, Gapex-5/RME-6. The VPS9 domain is a guanine nucleotide exchange factor for Rab31, a Rab5 subfamily GTPase implicated in trans-Golgi network (TGN)-to-endosome trafficking. Overexpression of Rab31 blocks insulin-stimulated Glut4 translocation, whereas knockdown of Rab31 potentiates insulin-stimulated Glut4 translocation and glucose uptake. Gapex-5 is predominantly cytosolic in untreated cells; its overexpression promotes intracellular retention of Glut4 in adipocytes. Insulin recruits the CIP4/Gapex-5 complex to the plasma membrane, thus reducing Rab31 activity and permitting Glut4 vesicles to translocate to the cell surface, where Glut4 docks and fuses to transport glucose into the cell.

MeSH Terms
Adipocytes/metabolism Amino Acid Sequence Animals Cell Line Cell Membrane/metabolism Fibroblasts/metabolism Glucose Transporter Type 4/metabolism Guanine Nucleotide Exchange Factors/chemistry,metabolism Insulin/metabolism Mice Microtubule-Associated Proteins/metabolism Minor Histocompatibility Antigens Molecular Sequence Data Protein Structure, Tertiary Protein Transport Sequence Alignment Two-Hybrid System Techniques rab5 GTP-Binding Proteins/metabolism
Chemicals
Glucose Transporter Type 4 Guanine Nucleotide Exchange Factors Insulin Microtubule-Associated Proteins Minor Histocompatibility Antigens Trip10 protein, mouse rab5 GTP-Binding Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Lodhi Irfan J
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Chiang Shian-Huey
Chang Louise
Vollenweider Daniel
Watson Robert T
Inoue Mayumi
Pessin Jeffrey E
Saltiel Alan R
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Article Info
Journal
Cell metabolism
Abbr.
Cell Metab
ISSN
1550-4131
DOI
10.1016/j.cmet.2006.12.006
Published
2007-01-00
Pages
59-72
Language
English
Region
United States
NLM ID
101233170
PMCID
PMC1779820
Subset
IM
Grants
NIDDK NIH HHS · DK59291 · United States
NIDDK NIH HHS · R01 DK059291 · United States
NIDDK NIH HHS · R01 DK061618 · United States
NIDDK NIH HHS · 5P60-DK20572 · United States
NIDDK NIH HHS · P60 DK020572 · United States
NIDDK NIH HHS · R01-DK061618 · United States
External Links
PubMed source DOI: 10.1016/j.cmet.2006.12.006 PMC Full Text View journal details
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