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  4. The developmental shift of NMDA receptor composition proceeds independently of the GluN2B CaMKII interaction site and distinct 2A/2B C-termini-directed events
 
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The developmental shift of NMDA receptor composition proceeds independently of the GluN2B CaMKII interaction site and distinct 2A/2B C-termini-directed events
File(s)
mmc2.pdf (4.46 MB)
Published version
Author(s)
McKay, Sean
Ryan, Tomás J
McQueen, Jamie
Indersmitten, Tim
Marwick, Katie FM
more
Type
Journal Article
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.
Date Issued
2018-10-23
Date Acceptance
2018-09-07
Citation
Cell Reports, 2018, 25 (4), pp.841-851.e4
URI
http://hdl.handle.net/10044/1/64525
DOI
https://www.dx.doi.org/10.1016/j.celrep.2018.09.089
ISSN
2211-1247
Publisher
Elsevier
Start Page
841
End Page
851.e4
Journal / Book Title
Cell Reports
Volume
25
Issue
4
Copyright Statement
© 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Publication Status
Published
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