Protein kinases and light: unlikely partners in a receptor localization puzzle.
Brief flashes of light directed at neuronal cell bodies and proximal dendrites of neurons in culture can enhance whole-cell electrophysiological responses mediated by NMDA and GABA(A) receptors. In experiments aimed at identifying the molecular moieties responsible for mediating this phenomenon, we observed that broad-spectrum protein kinase inhibitors substantially amplified the actions of light. Kinase inhibitors, however, were surprisingly ineffective in altering light-induced potentiation of recombinant NMDA receptors expressed in Chinese hamster ovary (CHO) cells. Furthermore, receptors assembled from truncated NMDA receptor subunits, previously shown to be relatively insensitive to modulation via phosphorylation, remained light sensitive. Phosphatase inhibitors had no effects of light-induced NMDA receptor potentiation in neurons, and nucleated patches excised from neuronal somata behaved similarly to CHO cells. Taken together, these data suggests that the effects of kinase inhibitors were unrelated to the molecular mechanism of light-induced potentiation. We propose a model whereby kinase inhibition promotes an enrichment of NMDA receptors in the neuronal cell body vs. the distal dendrites. Under these conditions, NMDA receptor redistribution elicited by kinase inhibitors would increase the number of receptors exposed to light and, as a consequence, the whole cell response. These observations support a critical role for protein kinases in the rapid redistribution of neurotransmitter receptors, with profound physiological significance.
Leszkiewicz
Daniel N
DN
Department of Neurobiology, University of Pittsburgh School of Medicine, E1456 BST, 15261, Pittsburgh, PA, USA.
McLaughlin
Beth Ann
BA
Aizenman
Elias
E
D000818:Animals; D016466:CHO Cells; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008027:Light; D009474:Neurons / Q000201:enzymology / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000528:radiation effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000528:radiation effects; D011994:Recombinant Proteins / Q000187:drug effects / Q000528:radiation effects
D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D011494:Protein Kinases