Insulin-like growth factor-1 increases activity and surface levels of the GLAST subtype of glutamate transporter.
Glutamate uptake systems are the primary mechanisms involved in excitatory amino acids clearance, their regulation is extremely important for proper neuronal function. Using cultured chick cerebellar Bergmann glia cells, the involvement of receptor tyrosine kinases in glutamate uptake was studied. Treatment of the cells with insulin-like growth factor-1 but not epidermal growth factor or neuronal growth factor, induces a dose and time dependent increase in [(3)H]-D-aspartate uptake that is sensitive to wortmannin, an inhibitor of phosphatidylinositol 3-kinase. Saturation experiments show a significant increase in V(max), suggesting that the amount of transporter molecules at the cell membrane under insulin-like growth factor-1 treatment is augmented. This interpretation was strengthen by equilibrium-binding experiments and by the fact that the increase in [(3)H]-D-aspartate uptake was not dependent on protein synthesis. The present studies suggest that insulin-like growth factor-1 signaling is involved in modulation of glutamate transporter cell surface expression.
Gamboa
Citlalli
C
Departamento de Genética y Biologija Molecular, Centro de Investigación y de Estudios, Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, México D.F 07000, Mexico.
Ortega
Arturo
A
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D026603:D-Aspartic Acid / Q000493:pharmacokinetics; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology
D027322:Amino Acid Transport System X-AG; D026603:D-Aspartic Acid; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases