NMDAR-Activated PP1 Dephosphorylates GluN2B to Modulate NMDAR Synaptic Content

0508602 - FGÚ 2020 RIV US eng J - Journal Article
Chiu, A. M. - Wang, J. - Fiske, M. P. - Hubálková, Pavla - Barse, L. - Gray, J. A. - Sanz-Clemente, A.
NMDAR-Activated PP1 Dephosphorylates GluN2B to Modulate NMDAR Synaptic Content.
Cell Reports. Roč. 28, č. 2 (2019), s. 332-341. ISSN 2211-1247. E-ISSN 2211-1247
Institutional support: RVO:67985823
Keywords : GluN2B * NMDA receptors * NMDAR synaptic content * PP1 * dephosphorylation * extrasynaptic NMDAR
OECD category: Neurosciences (including psychophysiology
Impact factor: 8.109, year: 2019
Method of publishing: Open access
https://doi.org/10.1016/j.celrep.2019.06.030

In mature neurons, postsynaptic N-methyl-D-aspartate receptors (NMDARs) are segregated into two populations, synaptic and extrasynaptic, which differ in localization, function, and associated intracellular cascades. These two pools are connected via lateral diffusion, and receptor exchange between them modulates synaptic NMDAR content. Here, we identify the phosphorylation of the PDZ-ligand of the GIuN2B subunit of NMDARs (at S1480) as a critical determinant in dynamically controlling NMDAR synaptic content. We find that phosphorylation of GIuN2B at S1480 maintains NMDARs at extrasynaptic membranes as part of a protein complex containing protein phosphatase 1 (PP1). Global activation of NMDARs leads to the activation of PP1, which mediates dephosphorylation of GluN2B at S1480 to promote an increase in synaptic NMDAR content. Thus, PP1-mediated dephosphorylation of the GIuN2B PDZ-ligand modulates the synaptic expression of NMDARs in mature neurons in an activity-dependent manner, a process with profound consequences for synaptic and structural plasticity, metaplasticity, and synaptic neurotrans-mission.
Permanent Link: http://hdl.handle.net/11104/0299462