Edinburgh Research Explorer

The developmental shift of NMDA receptor composition proceeds independently of GluN2 subunit-specific GluN2 C-terminal sequences

Research output: Contribution to journalArticle

Related Edinburgh Organisations

Open Access permissions

Open

Documents

Original languageEnglish
Pages (from-to)841-851.e4
JournalCell Reports
Volume25
Issue number4
Early online date23 Oct 2018
DOIs
StateE-pub ahead of print - 23 Oct 2018

Abstract

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.

Download statistics

No data available

ID: 75875129