Conventional kinesin KIF5B mediates insulin-stimulated GLUT4 movements on microtubules

Sabina Semiz, Jin G. Park, Sarah M.C. Nicoloro, Paul Furcinitti, Chuanyou Zhang, Anil Chawla, John Leszyk, Michael P. Czech

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2387-2399
Number of pages13
JournalEMBO Journal
Volume22
Issue number10
DOIs
StatePublished - May 15 2003

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Keywords

  • Adipocytes
  • GLUT4
  • Insulin
  • Kinesin
  • Microtubules

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Semiz, S., Park, J. G., Nicoloro, S. M. C., Furcinitti, P., Zhang, C., Chawla, A., Leszyk, J., & Czech, M. P. (2003). Conventional kinesin KIF5B mediates insulin-stimulated GLUT4 movements on microtubules. EMBO Journal, 22(10), 2387-2399. https://doi.org/10.1093/emboj/cdg237