Expression of a prenylation-deficient Rab4 inhibits the GLUT4 translocation induced by active phosphatidylinositol 3-kinase and protein kinase B.
The small GTPase Rab4 has been shown to participate in the subcellular distribution of GLUT4 under both basal and insulin-stimulated conditions in adipocytes. In the present work, we have characterized the effect of Rab4 DeltaCT, a prenylation-deficient and thus cytosolic form of Rab4, in this process. We show that the expression of Rab4 DeltaCT in freshly isolated adipocytes inhibits insulin-induced GLUT4 translocation, but only when this protein is in its GTP-bound active form. Further, it not only blocks the effect of insulin, but also that of a hyperosmotic shock, but does not interfere with the effect of zinc ions on GLUT4 translocation. Rab4 DeltaCT was then shown to prevent GLUT4 translocation induced by the expression of an active form of phosphatidylinositol 3-kinase or of protein kinase B, without altering the activities of the enzymes. Our results are consistent with a role of Rab4 DeltaCT acting as a dominant negative protein towards Rab4, possibly by binding to Rab4 effectors.
Cormont
M
M
INSERM E 99-11, Faculté de Médecine, Avenue de Vallombrose, 06107 Nice Cedex 02, France. cormont@unice.fr
Gautier
N
N
Ilc
K
K
le Marchand-Brustel
Y
Y
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D009154:Mutation; D009997:Osmotic Pressure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017368:Protein Prenylation; D017346:Protein Serine-Threonine Kinases; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology; D020695:rab4 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011993:Recombinant Fusion Proteins; D015032:Zinc; D020695:rab4 GTP-Binding Proteins; C495694:Slc2a4 protein, rat