CHARACTERIZATION OF MULTIPLE PHOSPHORYLATION SITES ON THE AMPA RECEPTOR GLUR1 SUBUNIT

We have characterized the phosphorylation of the glutamate receptor su bunit GluR1, using biochemical and electrophysiological techniques. Gl uR1 is phosphorylated on multiple sites that are all located on the C- terminus of the protein. Cyclic AMP-dependent protein kinase specifica lly phosphorylates SER-845 of GluR1 in transfected HEK cells and in ne urons in culture. Phosphorylation of this residue results in a 40% pot entiation of the peak current through GluR1 homo-meric channels. In ad dition, 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 p hosphorylation of this residue may underlie the PKA-induced potentiati on of AMPA receptors in neurons.