title: Evolution of GluN2A/B cytoplasmic domains diversified vertebrate synaptic plasticity and behavior.
abstract: Two genome duplications early in the vertebrate lineage expanded gene families, including GluN2 subunits of the NMDA receptor. Diversification between the four mammalian GluN2 proteins occurred primarily at their intracellular C-terminal domains (CTDs). To identify shared ancestral functions and diversified subunit-specific functions, we exchanged the exons encoding the GluN2A (also known as Grin2a) and GluN2B (also known as Grin2b) CTDs in two knock-in mice and analyzed the mice's biochemistry, synaptic physiology, and multiple learned and innate behaviors. The eight behaviors were genetically separated into four groups, including one group comprising three types of learning linked to conserved GluN2A/B regions. In contrast, the remaining five behaviors exhibited subunit-specific regulation. GluN2A/B CTD diversification conferred differential binding to cytoplasmic MAGUK proteins and differential forms of long-term potentiation. These data indicate that vertebrate behavior and synaptic signaling acquired increased complexity from the duplication and diversification of ancestral GluN2 genes.
authors.affiliation: Genes to Cognition Programme, Wellcome Trust Sanger Institute, Cambridge, UK.
authors.forename: Tomás J
authors.initials: TJ
authors.lastname: Ryan
authors.forename: Maksym V
authors.initials: MV
authors.lastname: Kopanitsa
authors.forename: Tim
authors.initials: T
authors.lastname: Indersmitten
authors.forename: Jess
authors.initials: J
authors.lastname: Nithianantharajah
authors.forename: Nurudeen O
authors.initials: NO
authors.lastname: Afinowi
authors.forename: Charles
authors.initials: C
authors.lastname: Pettit
authors.forename: Lianne E
authors.initials: LE
authors.lastname: Stanford
authors.forename: Rolf
authors.initials: R
authors.lastname: Sprengel
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Saksida
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bussey
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: O'Dell
authors.forename: Seth G N
authors.initials: SG
authors.lastname: Grant
authors.forename: Noboru H
authors.initials: NH
authors.lastname: Komiyama
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001703:Biophysics; D003593:Cytoplasm / Q000378:metabolism*; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells; D004644:Emotions / Q000502:physiology; D019143:Evolution, Molecular; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics; D007858:Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009042:Motivation / Q000235:genetics; D009043:Motor Activity / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010641:Phenotype; D017434:Protein Structure, Tertiary / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor