Site-specific phosphorylation of PSD-95 dynamically regulates the postsynaptic density as observed by phase separation.

ABSTRACT: Postsynaptic density protein 95 is a key scaffolding protein in the postsynaptic density of excitatory glutamatergic neurons, organizing signaling complexes primarily via its three PSD-95/Discs-large/Zona occludens domains. PSD-95 is regulated by phosphorylation, but technical challenges have limited studies of the molecular details. Here, we genetically introduced site-specific phosphorylations in single, tandem, and full-length PSD-95 and generated a total of 11 phosphorylated protein variants. We examined how these phosphorylations affected binding to known interaction partners and the impact on phase separation of PSD-95 complexes and identified two new phosphorylation sites with opposing effects. Phosphorylation of Ser78 inhibited phase separation with the glutamate receptor subunit G

SUBMITTER: Vistrup-Parry M 

PROVIDER: S-EPMC8567388 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature