Regulation of kainate receptors by protein kinase C and metabotropic glutamate receptors.
Kainate receptors have recently been shown to be involved in synaptic transmission, to regulate transmitter release and to mediate synaptic plasticity in different regions of the CNS. However, very little is known about endogenous mechanisms that can control native kainate receptor signalling. In this study we have found that GluR5-containing kainate receptor-mediated actions can be modulated by activation of protein kinase C (PKC) but not protein kinase A (PKA). However, both PKA and PKC directly phosphorylate the GluR5 subunit of kainate receptors. Metabotropic glutamate (mGlu) receptors are well known to be involved in synaptic transmission, regulation of transmitter release and synaptic plasticity in a variety of brain regions. We now demonstrate that kainate receptor signalling is enhanced by activation of group I mGlu receptors, in a PKC-dependent manner. These data demonstrate for the first time that kainate receptor function can be modulated by activation of metabotropic glutamate receptors and have implications for understanding mechanisms of synaptic transmission, plasticity and disorders such as epilepsy.
Cho
Kwangwook
K
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1TD, UK.
Francis
Joanna C
JC
Hirbec
Hélène
H
Dev
Kumlesh
K
Brown
Malcolm W
MW
Henley
Jeremy M
JM
Bashir
Zafar I
ZI
D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D005971:Glutamates; D005982:Glutathione Transferase; D005998:Glycine; D010648:Phenylacetates; D011493:Protein Kinase C; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; C107349:2-chloro-5-hydroxyphenylglycine; C046105:4-methylglutamic acid