PSD-95 Serine 73 phosphorylation is not required for induction of NMDA-LTD.

Agata Nowacka, Małgorzata Borczyk, Ahmad Salamian, Tomasz Wójtowicz, Jakub Włodarczyk, Kasia Radwanska
Sci Rep. 2020-02-06; 10(1):
DOI: 10.1038/s41598-020-58989-2

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PSD-95 is a major scaffolding protein of the post-synaptic density (PSD) of a glutamatergic synapse. PSD-95, via interactions with stargazin, anchors AMPA receptors at the synapse and regulates AMPAR currents. The expression of PSD-95 is regulated during synaptic plasticity. It is, however, unknown whether this regulation is required for induction of functional plasticity of glutamatergic synapses. Here, we show that NMDA-induced long-term depression of synaptic transmission (NMDA-LTD) is accompanied by downregulation of PSD-95 protein levels. Using pharmacologic and molecular manipulations, we further demonstrate that the NMDA-induced downregulation of PSD-95 depends on the activation of CaMKII and CaMKII-driven phosphorylation of PSD-95 serine 73. Surprisingly, neither CaMKII activity nor CaMKII-dependent phosphorylation of PSD-95 serine 73 are required for the expression of NMDA-LTD. These results support the hypothesis that synaptic plasticity of AMPARs may occur without dynamic regulation of PSD-95 protein levels.

Auteurs Bordeaux Neurocampus