Metabotropic glutamate and dopamine receptors co‐regulate AMPA receptor activity through PKA in cultured chick retinal neurones: effect on GluR4 phosphorylation and surface expression

Abstract

Glutamate receptor phosphorylation has been implicated in several forms of modulation of synaptic transmission. It has been reported that protein kinase A (PKA) can phosphorylate the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit GluR4 on Ser842, both in vitro and in vivo. Here, we studied the regulation of GluR4 phosphorylation and intracellular trafficking by PKA and by metabotropic receptors coupled to adenylyl cyclase (AC), in cultured chick retinal amacrine-like neurones, which are enriched in GluR4. The regulation of AMPA receptor activity by PKA and by metabotropic AC-coupled receptors was also investigated by measuring the [Ca 2+ ] i response to kainate in Na + -free medium. Stimulation of AC with forskolin (FSK), or using the selective agonist of dopamine D 1 receptors (±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF38393), increased the [Ca 2+ ] i response to kainate, GluR4 phosphorylation at Ser842 and GluR4 surface expression. Pre-incubation of the cells with (2S,2¢R,3¢R)-2-(2¢,3¢-dicarboxycyclopropyl)glycine (DCG-IV), an agonist of group II metabotropic glutamate receptors (mGluR), which are coupled to inhibition of AC, inhibited the effect of FSK and of SKF38393 on AMPA receptor activity, GluR4 phosphorylation and expression at the plasma membrane. These results indicate that there is a functional cross-talk between dopamine D 1 receptors and group II mGluR in the regulation of GluR4 phosphorylation and AMPA receptor activity. Our data show that GluR4 phosphorylation at Ser842 by PKA, and its recruitment to the plasma membrane upon phosphorylation, is regulated by metabotropic receptors.

Synaptic localization of GluR4-containing AMPARs and Arc during acquisition, extinction, and reacquisition of in vitro classical conditioning

“…Consistent with these results, characterization of GluR4 subunits has revealed phosphorylation sites within the C-terminal domain of Ser 842 by CaMKII, PKA and PKC, Thr 830 by PKC in vitro, as well as phosphorylation in transfected cells of Ser 842 by PKA (Carvalho, Kameyama, & Huganir, 1999). Phosphorylation actively recruits the surface expression of GluR4-containing AMPARs in cell cultures (Gomes, Correia, Esteban, Duarte, & Carvalho, 2007;Gomes, Cunha, Nuriya, Faro, Huganir, Pires, Carvalho, & Duarte, 2004;Esteban, Shi, Wilson, Nuyriya, Huganir, & Malinow, 2003), possibly through interactions with the 4.1 family of proteins (Coleman, Mottershead, Haapalahti, & Keinanen, 2003), Arc see below), and the actin cytoskeleton.…”

Protein-Protein Coupling/Uncoupling Enables Dopamine D2Receptor Regulation of AMPA Receptor-Mediated Excitotoxicity

“…AMPA receptors are ligand-gated ion channels that are classically regulated by G-protein-coupled receptors through the activation of downstream second-messenger systems, which can involve the phosphorylation of the ligand-gated ion channel (Price et al, 1999;Snyder et al, 2000;Chao et al, 2002Chao et al, , 2003Vanhoose and Winder, 2003;Gomes et al, 2004;Mangiavacchi and Wolf, 2004). Recently, our group has demonstrated that G-proteincoupled dopamine D 1 /D 5 receptors can modulate ligand-gated ion channel NMDA/GABA A receptors through direct proteinprotein interactions, respectively (Liu et al, 2000;Lee et al, 2002a;Pei et al, 2004).…”

Brain-derived Neurotrophic Factor Regulates the Expression and Synaptic Delivery ofα-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor Subunits in Hippocampal Neurons

“…The relative changes in the mRNA levels of glutamate receptor subunits in cultured hippocampal neurons were determined using the (27). The non-bound biotin was removed by washing the cells with phosphate-buffered saline containing 100 mM glycine.…”