TY - JOUR T1 - Regulation of GluA1 <em>α</em>-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Function by Protein Kinase C at Serine-818 and Threonine-840 JF - Molecular Pharmacology JO - Mol Pharmacol SP - 618 LP - 629 DO - 10.1124/mol.113.091488 VL - 85 IS - 4 AU - Meagan A. Jenkins AU - Gordon Wells AU - Julia Bachman AU - James P. Snyder AU - Andrew Jenkins AU - Richard L. Huganir AU - Robert E. Oswald AU - Stephen F. Traynelis Y1 - 2014/04/01 UR - http://molpharm.aspetjournals.org/content/85/4/618.abstract N2 - Three residues within the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunit GluA1 C terminus (Ser818, Ser831, Thr840) can be phosphorylated by Ca2+/phospholipid-dependent protein kinase (PKC). Here, we show that PKC phosphorylation of GluA1 Ser818 or Thr840 enhances the weighted mean channel conductance without altering the response time course or agonist potency. These data support the idea that these residues constitute a hyper-regulatory domain for the AMPA receptor. Introduction of phosphomimetic mutations increases conductance only at these three sites within the proximal C terminus, consistent with a structural model with a flexible linker connecting the distal C-terminal domain to the more proximal domain containing a helix bracketed by Ser831 and Thr840. NMR spectra support this model and raise the possibility that phosphorylation can alter the configuration of this domain. Our findings provide insight into the structure and function of the C-terminal domain of GluA1, which controls AMPA receptor function and trafficking during synaptic plasticity in the central nervous system. ER -