title: GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses.
abstract: Presynaptic ionotropic glutamate receptors are emerging as key players in the regulation of synaptic transmission. Here we identify GluR7, a kainate receptor (KAR) subunit with no known function in the brain, as an essential subunit of presynaptic autoreceptors that facilitate hippocampal mossy fiber synaptic transmission. GluR7(-/-) mice display markedly reduced short- and long-term synaptic potentiation. Our data suggest that presynaptic KARs are GluR6/GluR7 heteromers that coassemble and are localized within synapses. We show that recombinant GluR6/GluR7 KARs exhibit low sensitivity to glutamate, and we provide evidence that presynaptic KARs at mossy fiber synapses are likely activated by high concentrations of glutamate. Overall, from our data, we propose a model whereby presynaptic KARs are localized in the presynaptic active zone close to release sites, display low affinity for glutamate, are likely Ca(2+)-permeable, are activated by single release events, and operate within a short time window to facilitate the subsequent release of glutamate.
authors.affiliation: Laboratoire Physiologie Cellulaire de la Synapse, Centre National de la Recherche Scientifique, Bordeaux Neuroscience Institute, University of Bordeaux, 33077 Bordeaux Cedex, France.
authors.forename: Paulo S
authors.initials: PS
authors.lastname: Pinheiro
authors.forename: David
authors.initials: D
authors.lastname: Perrais
authors.forename: Françoise
authors.initials: F
authors.lastname: Coussen
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bettler
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Mann
authors.forename: João O
authors.initials: JO
authors.lastname: Malva
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Heinemann
authors.forename: Christophe
authors.initials: C
authors.lastname: Mulle
mesh_terms: D000818:Animals; D017660:Autoreceptors / Q000378:metabolism*; D002460:Cell Line; D019706:Excitatory Postsynaptic Potentials; D006801:Humans; D017774:Long-Term Potentiation; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport; D018092:Kainic Acid Receptors / Q000172:deficiency / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D000097806:GluK2 Kainate Receptor; D000097808:GluK3 Kainate Receptor
chemical_list: D017660:Autoreceptors; D021122:Protein Subunits; D018092:Kainic Acid Receptors; D011994:Recombinant Proteins; D000097806:GluK2 Kainate Receptor; D000097808:GluK3 Kainate Receptor