Expression of a prenylation-deficient Rab4 inhibits the GLUT4 translocation induced by active phosphatidylinositol 3-kinase and protein kinase B

The Biochemical Journal
M CormontY Le Marchand-Brustel

Abstract

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.

References

Feb 1, 1994·European Journal of Biochemistry·M CormontY Le Marchand-Brustel
Apr 1, 1993·The Journal of Clinical Investigation·S J HeydrickY Le Marchand-Brustel
May 1, 1997·Endocrinology·J F TantiY Le Marchand-Brustel
Oct 27, 1997·The Journal of Biological Chemistry·D ChenJ E Pessin
Dec 14, 1999·Molecular and Cellular Biology·M Hashiramoto, D E James
Nov 7, 2000·The Journal of Biological Chemistry·L LiH Shibata
Feb 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·M CormontY Le Marchand-Brustel

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Citations

Nov 1, 2001·Proceedings of the National Academy of Sciences of the United States of America·J HuangJ M Olefsky
Aug 24, 2010·Journal of Molecular and Cellular Cardiology·Sharon EtzionAnthony J Muslin
Sep 22, 2010·Journal of Cellular Physiology·Jung Ok LeeHyeon Soo Kim
Jan 4, 2006·Biochemical and Biophysical Research Communications·Sunil K SaxenaConstantine George
Dec 15, 2010·Seminars in Cell & Developmental Biology·Shreya MitraGordon B Mills

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