title: A proteomic analysis reveals the interaction of GluK1 ionotropic kainate receptor subunits with Go proteins.
abstract: Kainate receptors (KARs) are found ubiquitously in the CNS and are present presynaptically and postsynaptically regulating synaptic transmission and excitability. Functional studies have proven that KARs act as ion channels as well as potentially activating G-proteins, thus indicating the existance of a dual signaling system for KARs. Nevertheless, it is not clear how these ion channels activate G-proteins and which of the KAR subunits is involved. Here we performed a proteomic analysis to define proteins that interact with the C-terminal domain of GluK1 and we identified a variety of proteins with many different functions, including a Go α subunit. These interactions were verified through distinct in vitro and in vivo assays, and the activation of the Go protein by GluK1 was validated in bioluminescence resonance energy transfer experiments, while the specificity of this association was confirmed in GluK1-deficient mice. These data reveal components of the KAR interactome, and they show that GluK1 and Go proteins are natural partners, accounting for the metabotropic effects of KARs.
authors.affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas, Universidad Miguel Hernández, 03550 San Juan de Alicante, Spain, and.
authors.forename: Izabela
authors.identifier: http://orcid.org/0000-0003-0799-3327
authors.initials: I
authors.lastname: Rutkowska-Wlodarczyk
authors.affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas, Universidad Miguel Hernández, 03550 San Juan de Alicante, Spain, and.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Aller
authors.affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas, Universidad Miguel Hernández, 03550 San Juan de Alicante, Spain, and.
authors.forename: Sergio
authors.initials: S
authors.lastname: Valbuena
authors.affiliation: Institut de Génomique Fonctionnelle, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, 34094 Montpellier cedex 5, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Bologna
authors.affiliation: Institut de Génomique Fonctionnelle, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, 34094 Montpellier cedex 5, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Prézeau
authors.affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas, Universidad Miguel Hernández, 03550 San Juan de Alicante, Spain, and jlerma@umh.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Lerma
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021122:Protein Subunits; D040901:Proteomics; D018092:Kainic Acid Receptors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007608:Kainic Acid; D021122:Protein Subunits; D018092:Kainic Acid Receptors
keywords: GluK1; Go protein; kainate receptors; metabotropic; noncanonical; proteomics
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