Phosphorylation and Modulation of a Kainate Receptor (GluR6) by cAMP- Dependent Protein Kinase

• Published in: Science (American Association for the Advancement of Science) Vol. 259; no. 5098; pp. 1173 - 1175
• Main Authors: Wang, Lu-Yang, Taverna, Franco A., Huang, Xi-Ping, MacDonald, John F., Hampson, David R.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 19.02.1993; American Association for the Advancement of Science
• Subjects: Agonists; Amino Acid Sequence; Aminoacid receptors (glycine, glutamate, gaba); Base Sequence; Binding Sites; Biological and medical sciences; Biological response modifiers; Brain; Brain - physiology; Cell receptors; Cell structures and functions; cells; Cells, Cultured; Concanavalin A - pharmacology; Evoked Potentials - drug effects; Fundamental and applied biological sciences. Psychology; Glutamate; Glutamate receptors; glutamic acid GluR6; Humans; Inurement; Kainic Acid - pharmacology; Kidney; Kinetics; Lectins; man; Membrane Potentials - drug effects; modulation; Molecular and cellular biology; Molecular Sequence Data; Mutagenesis, Site-Directed; Neurons; Oligodeoxyribonucleotides; Perfusion; Phosphorylation; Physiological aspects; Physiological regulation; protein kinase; Protein kinases; Protein Kinases - metabolism; Receptors; Receptors, Glutamate - drug effects; Receptors, Glutamate - genetics; Receptors, Glutamate - physiology; Receptors, Kainic Acid; Serine; site-directed mutagenesis; Wheat Germ Agglutinins - pharmacology; Human; Embryo; Regulation(control); Enzyme; Perfusion; Protein kinase; Site directed mutagenesis; Glutamate receptor; Kidney; Dose activity relation; Kainate receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8382377

Ligand-gated ion channels gated by glutamate constitute the major excitatory neurotransmitter system in the mammalian brain. The functional modulation of GluR6, a kainate-activated glutamate receptor, by adenosine 3′,5′-monophosphate-dependent protein kinase A (PKA) was examined with receptors expressed in human embryonic kidney cells. Kainate-evoked currents underwent a rapid desensitization that was blocked by lectins. Kainate currents were potentiated by intracellular perfusion of PKA, and this potentiation was blocked by co-application of an inhibitory peptide. Site-directed mutagenesis was used to identify the site or sites of phosphorylation on GluR6. Although mutagenesis of two serine residues, Ser$^{684}$ and Ser$^{666}$, was required for complete abolition of the PKA-induced potentiation, Ser$^{684}$ may be the preferred site of phosphorylation in native GluR6 receptor complexes. These results indicate that glutamate receptor function can be directly modulated by protein phosphorylation and suggest that a dynamic regulation of excitatory receptors could be associated with some forms of learning and memory in the mammalian brain.