Title
Conventional kinesin KIF5B mediates insulin-stimulated GLUT4 movements on microtubules
UMMS Affiliation
Graduate School of Biomedical Sciences; Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology
Publication Date
2003-05-14
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
10.1093/emboj/cdg237
Source
EMBO J. 2003 May 15;22(10):2387-99. Link to article on publisher's site
Journal/Book/Conference Title
The EMBO journal
Related Resources
PubMed ID
12743033
Repository Citation
Semiz S, Park JG, Nicoloro SM, Furcinitti PS, Zhang C, Chawla A, Leszyk JD, Czech MP. (2003). Conventional kinesin KIF5B mediates insulin-stimulated GLUT4 movements on microtubules. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1093/emboj/cdg237. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1095