Conventional kinesin KIF5B mediates insulin-stimulated GLUT4 movements on microtubules

Autor: Chuanyou Zhang, Jin Park, Anil Chawla, Sabina Semiz, Paul S. Furcinitti, Michael P. Czech, Sarah M. Nicoloro, John D. Leszyk
Rok vydání: 2003
Předmět:
Monosaccharide Transport Proteins
Recombinant Fusion Proteins
medicine.medical_treatment
Glucose uptake
Molecular Sequence Data
Kinesins
Muscle Proteins
macromolecular substances
Microtubules
General Biochemistry
Genetics and Molecular Biology
Wortmannin
Mice
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
Bacterial Proteins
Microtubule
Adipocytes
medicine
Animals
Insulin
Enzyme Inhibitors
Transport Vesicles
Molecular Biology
Cells
Cultured
Oligonucleotide Array Sequence Analysis
Glucose Transporter Type 4
General Immunology and Microbiology
biology
General Neuroscience
Cell Membrane
Glucose transporter
Biological Transport
Articles
Intracellular Membranes
Fibroblasts
Rats
Cell biology
Androstadienes
Luminescent Proteins
Insulin receptor
chemistry
biology.protein
Kinesin
hormones
hormone substitutes
and hormone antagonists
GLUT4
Signal Transduction
Zdroj: The EMBO Journal. 22:2387-2399
ISSN: 1460-2075
DOI: 10.1093/emboj/cdg237
Popis: 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.
Databáze: OpenAIRE
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