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The Developmental Shift of NMDA Receptor Composition Proceeds Independently of GluN2 Subunit-Specific GluN2 C-Terminal Sequences.
McKay, Sean; Ryan, Tomás J; McQueen, Jamie; Indersmitten, Tim; Marwick, Katie F M; Hasel, Philip; Kopanitsa, Maksym V; Baxter, Paul S; Martel, Marc-André; Kind, Peter C; Wyllie, David J A; O'Dell, Thomas J; Grant, Seth G N; Hardingham, Giles E; Komiyama, Noboru H.
Affiliation
  • McKay S; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; UK Dementia Research Institute at the University
  • Ryan TJ; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia.
  • McQueen J; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; UK Dementia Research Institute at the University
  • Indersmitten T; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Marwick KFM; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
  • Hasel P; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; UK Dementia Research Institute at the University
  • Kopanitsa MV; The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; UK Dementia Research Institute at Imperial College London, Hammersmith Hospital Campus, Imperial College, London W12 0NN, UK.
  • Baxter PS; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; UK Dementia Research Institute at the University
  • Martel MA; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
  • Kind PC; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
  • Wyllie DJA; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
  • O'Dell TJ; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Grant SGN; Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; Centre for Clinical Brain Sciences, University of Edinburgh Chancellor's Building, Edinburgh, UK.
  • Hardingham GE; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; UK Dementia Research Institute at the University
  • Komiyama NH; Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; Centre for Clinical Brain Sciences, University of Edinburgh Chancellor's Building, Edinburgh, UK. Electronic add
Cell Rep ; 25(4): 841-851.e4, 2018 10 23.
Article in En | MEDLINE | ID: mdl-30355491
The GluN2 subtype (2A versus 2B) determines biophysical properties and signaling of forebrain NMDA receptors (NMDARs). During development, GluN2A becomes incorporated into previously GluN2B-dominated NMDARs. This "switch" is proposed to be driven by distinct features of GluN2 cytoplasmic C-terminal domains (CTDs), including a unique CaMKII interaction site in GluN2B that drives removal from the synapse. However, these models remain untested in the context of endogenous NMDARs. We show that, although mutating the endogenous GluN2B CaMKII site has secondary effects on GluN2B CTD phosphorylation, the developmental changes in NMDAR composition occur normally and measures of plasticity and synaptogenesis are unaffected. Moreover, the switch proceeds normally in mice that have the GluN2A CTD replaced by that of GluN2B and commences without an observable decline in GluN2B levels but is impaired by GluN2A haploinsufficiency. Thus, GluN2A expression levels, and not GluN2 subtype-specific CTD-driven events, are the overriding factor in the developmental switch in NMDAR composition.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, N-Methyl-D-Aspartate Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cell Rep Year: 2018 Document type: Article Country of publication: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, N-Methyl-D-Aspartate Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cell Rep Year: 2018 Document type: Article Country of publication: Estados Unidos