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| Subject Categories: Membranes & Transport | Cellular Metabolism |
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| The EMBO Journal
(2003) 22, 2387–2399, doi:10.1093/emboj/cdg237 |
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| Conventional kinesin KIF5B mediates insulin-stimulated GLUT4 movements on microtubules |
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| Sabina Semiz1, 2, Jin G. Park1, 2, Sarah M.C. Nicoloro1, Paul Furcinitti1, Chuanyou Zhang1, Anil Chawla1, John Leszyk1 and Michael P. Czech1 |
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1 Program in Molecular Medicine, 373 Plantation Street, University of Massachusetts Medical School, Worcester, MA 01605, USA 2 S.Semiz and J.G.Park contributed equally to this work To whom correspondence should be addressed Michael P. Czech, Michael.Czech@umassmed.edu Received 13 August 2002; Revised 9 January 2003; Accepted 19 March 2003. |
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| Abstract |
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| Insulin stimulates glucose uptake in muscle and adipose cells by mobilizing intracellular membrane vesicles containing GLUT4 glucose transporter proteins to the plasma membrane. Here we show in live cultured adipocytes that intracellular membranes containing GLUT4–yellow fluorescent protein (YFP) move along tubulin–cyan fluorescent protein-labeled microtubules in response to insulin by a mechanism that is insensitive to the phosphatidylinositol 3 (PI3)-kinase inhibitor wortmannin. Insulin increased by several fold the observed frequencies, but not velocities, of long-range movements of GLUT4–YFP on microtubules, both away from and towards the perinuclear region. Genomics screens show conventional kinesin KIF5B is highly expressed in adipocytes and this kinesin is partially co-localized with perinuclear GLUT4. Dominant-negative mutants of conventional kinesin light chain blocked outward GLUT4 vesicle movements and translocation of exofacial Myc-tagged GLUT4–green fluorescent protein to the plasma membrane in response to insulin. These data reveal that insulin signaling targets the engagement or initiates the movement of GLUT4-containing membranes on microtubules via conventional kinesin through a PI3-kinase-independent mechanism. This insulin signaling pathway regulating KIF5B function appears to be required for GLUT4 translocation to the plasma membrane. |
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| Keywords: adipocytes, GLUT4, insulin, kinesin, microtubules |
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