Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Pharmacol
2013 Jan 01;831:106-21. doi: 10.1124/mol.112.081802.
Show Gene links
Show Anatomy links
Activation of group I metabotropic glutamate receptors potentiates heteromeric kainate receptors.
Rojas A
,
Wetherington J
,
Shaw R
,
Serrano G
,
Swanger S
,
Dingledine R
.
???displayArticle.abstract???
Kainate receptors (KARs), a family of ionotropic glutamate receptors, are widely expressed in the central nervous system and are critically involved in synaptic transmission. KAR activation is influenced by metabotropic glutamate receptor (mGlu) signaling, but the underlying mechanisms are not understood. We undertook studies to examine how mGlu modulation affects activation of KARs. Confocal immunohistochemistry of rat hippocampus and cultured rat cortex revealed colocalization of the high-affinity KAR subunits with group I mGlu receptors. In hippocampal and cortical cultures, the calcium signal caused by activation of native KARs was potentiated by activation of group I mGlu receptors. In Xenopus laevis oocytes, activation of group I mGlu receptors potentiated heteromeric but not homomeric KAR-mediated currents, with no change in agonist potency. The potentiation of heteromeric KARs by mGlu1 activation was attenuated by GDPβS, blocked by an inhibitor of phospholipase C or the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), prolonged by the phosphatase inhibitor okadaic acid, but unaffected by the tyrosine kinase inhibitor lavendustin A. Protein kinase C (PKC) inhibition reduced the potentiation by mGlu1 of GluK2/GluK5, and conversely, direct activation of PKC by phorbol 12-myristate,13-acetate potentiated GluK2/GluK5. Using site-directed mutagenesis, we identified three serines (Ser833, Ser836, and Ser840) within the membrane proximal region of the GluK5 C-terminal domain that, in combination, are required for mGlu1-mediated potentiation of KARs. Together, these data suggest that phosphorylation of key residues in the C-terminal domain changes the overall charge of this domain, resulting in potentiated agonist responses.
Akiyama,
Genistein, a specific inhibitor of tyrosine-specific protein kinases.
1987, Pubmed
Akiyama,
Genistein, a specific inhibitor of tyrosine-specific protein kinases.
1987,
Pubmed
Alt,
Pharmacological characterization of glutamatergic agonists and antagonists at recombinant human homomeric and heteromeric kainate receptors in vitro.
2004,
Pubmed
Aniksztejn,
Quisqualate Metabotropic Receptors Modulate NMDA Currents and Facilitate Induction of Long-Term Potentiation Through Protein Kinase C.
1992,
Pubmed
Anwyl,
Synaptic plasticity. A molecular switch for memory.
1994,
Pubmed
Anwyl,
Metabotropic glutamate receptors: electrophysiological properties and role in plasticity.
1999,
Pubmed
Bahn,
Kainate receptor gene expression in the developing rat brain.
1994,
Pubmed
Berthele,
Differential expression of rat and human type I metabotropic glutamate receptor splice variant messenger RNAs.
1998,
Pubmed
Besheer,
Pharmacological and anatomical evidence for an interaction between mGluR5- and GABA(A) alpha1-containing receptors in the discriminative stimulus effects of ethanol.
2005,
Pubmed
Bettler,
Review: neurotransmitter receptors. II. AMPA and kainate receptors.
1995,
Pubmed
Bortolotto,
Roles of metabotropic glutamate receptors in LTP and LTD in the hippocampus.
1999,
Pubmed
Bortolotto,
Kainate receptors are involved in synaptic plasticity.
1999,
Pubmed
Bureau,
Kainate receptor-mediated responses in the CA1 field of wild-type and GluR6-deficient mice.
1999,
Pubmed
Chamberlain,
SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity.
2012,
Pubmed
Chen,
Protein tyrosine kinase-mediated potentiation of currents from cloned NMDA receptors.
1996,
Pubmed
,
Xenbase
Chittajallu,
Regulation of glutamate release by presynaptic kainate receptors in the hippocampus.
1996,
Pubmed
Cho,
Regulation of kainate receptors by protein kinase C and metabotropic glutamate receptors.
2003,
Pubmed
Clarke,
A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission.
1997,
Pubmed
Darstein,
Distribution of kainate receptor subunits at hippocampal mossy fiber synapses.
2003,
Pubmed
Dascal,
Signalling via the G protein-activated K+ channels.
1997,
Pubmed
DeWire,
Beta-arrestins and cell signaling.
2007,
Pubmed
Donevan,
The methylglutamate, SYM 2081, is a potent and highly selective agonist at kainate receptors.
1998,
Pubmed
,
Xenbase
Egebjerg,
Ca2+ permeability of unedited and edited versions of the kainate selective glutamate receptor GluR6.
1993,
Pubmed
,
Xenbase
Ferraguti,
Immunohistochemical localization of the mGluR1beta metabotropic glutamate receptor in the adult rodent forebrain: evidence for a differential distribution of mGluR1 splice variants.
1998,
Pubmed
Geissler,
Thiazolidine-diones. Biochemical and biological activity of a novel class of tyrosine protein kinase inhibitors.
1990,
Pubmed
Harvey,
Signal transduction pathways involved in the acute potentiation of NMDA responses by 1S,3R-ACPD in rat hippocampal slices.
1993,
Pubmed
Hirbec,
Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP.
2003,
Pubmed
Huettner,
Kainate receptors and synaptic transmission.
2003,
Pubmed
Isaac,
Kainate receptor trafficking: physiological roles and molecular mechanisms.
2004,
Pubmed
Jiang,
Neuroprotection by selective allosteric potentiators of the EP2 prostaglandin receptor.
2010,
Pubmed
Kawajiri,
Multiple structural determinants of voltage-dependent magnesium block in recombinant NMDA receptors.
1993,
Pubmed
,
Xenbase
Kelso,
Protein kinase C-mediated enhancement of NMDA currents by metabotropic glutamate receptors in Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Kleckner,
Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes.
1988,
Pubmed
,
Xenbase
Konopacki,
Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis.
2011,
Pubmed
Kornreich,
Identification of C-terminal domain residues involved in protein kinase A-mediated potentiation of kainate receptor subtype 6.
2007,
Pubmed
Köhr,
Subtype-specific regulation of recombinant NMDA receptor-channels by protein tyrosine kinases of the src family.
1996,
Pubmed
Lerma,
Molecular physiology of kainate receptors.
2001,
Pubmed
Lerma,
Roles and rules of kainate receptors in synaptic transmission.
2003,
Pubmed
Mott,
Subunit-specific desensitization of heteromeric kainate receptors.
2010,
Pubmed
,
Xenbase
Mott,
pH-dependent inhibition of kainate receptors by zinc.
2008,
Pubmed
,
Xenbase
Nasu-Nishimura,
Differential regulation of kainate receptor trafficking by phosphorylation of distinct sites on GluR6.
2010,
Pubmed
Paternain,
GluR5 and GluR6 kainate receptor subunits coexist in hippocampal neurons and coassemble to form functional receptors.
2000,
Pubmed
Raymond,
Phosphorylation and modulation of recombinant GluR6 glutamate receptors by cAMP-dependent protein kinase.
1993,
Pubmed
Raymond,
Glutamate receptor modulation by protein phosphorylation.
1994,
Pubmed
Rivera,
PKC-dependent autoregulation of membrane kainate receptors.
2007,
Pubmed
Rodríguez-Moreno,
Kainate receptors presynaptically downregulate GABAergic inhibition in the rat hippocampus.
1997,
Pubmed
Ruiz,
Distinct subunits in heteromeric kainate receptors mediate ionotropic and metabotropic function at hippocampal mossy fiber synapses.
2005,
Pubmed
Schiffer,
Rat GluR7 and a carboxy-terminal splice variant, GluR7b, are functional kainate receptor subunits with a low sensitivity to glutamate.
1997,
Pubmed
Selak,
A role for SNAP25 in internalization of kainate receptors and synaptic plasticity.
2009,
Pubmed
Simonyi,
Expression of groups I and II metabotropic glutamate receptors in the rat brain during aging.
2005,
Pubmed
Sommer,
A glutamate receptor channel with high affinity for domoate and kainate.
1992,
Pubmed
Traynelis,
Glutamate receptor ion channels: structure, regulation, and function.
2010,
Pubmed
Traynelis,
Control of rat GluR6 glutamate receptor open probability by protein kinase A and calcineurin.
1997,
Pubmed
Wang,
Phosphorylation and modulation of a kainate receptor (GluR6) by cAMP-dependent protein kinase.
1993,
Pubmed
Wang,
Regulation of NMDA receptors by tyrosine kinases and phosphatases.
1994,
Pubmed
Wenthold,
Biochemical and assembly properties of GluR6 and KA2, two members of the kainate receptor family, determined with subunit-specific antibodies.
1994,
Pubmed