title: Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit.
abstract: We have characterized the phosphorylation of the glutamate receptor subunit GluR1, using biochemical and electrophysiological techniques. GluR1 is phosphorylated on multiple sites that are all located on the C-terminus of the protein. Cyclic AMP-dependent protein kinase specifically phosphorylates SER-845 of GluR1 in transfected HEK cells and in neurons in culture. Phosphorylation of this residue results in a 40% potentiation of the peak current through GluR1 homomeric channels. In addition, protein kinase C specifically phosphorylates Ser-831 of GluR1 in HEK-293 cells and in cultured neurons. These results are consistent with the recently proposed transmembrane topology models of glutamate receptors, in which the C-terminus is intracellular. In addition, the modulation of GluR1 by PKA phosphorylation of Ser-845 suggests that phosphorylation of this residue may underlie the PKA-induced potentiation of AMPA receptors in neurons.
authors.affiliation: Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: Roche
authors.forename: R J
authors.initials: RJ
authors.lastname: O'Brien
authors.forename: A L
authors.initials: AL
authors.lastname: Mammen
authors.forename: J
authors.initials: J
authors.lastname: Bernhardt
authors.forename: R L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA