AI Article Synopsis
- PSD-95 is an important protein in neurons that helps organize signaling structures, and its function is influenced by phosphorylation, although studying this has been challenging.
- Researchers introduced specific phosphorylation sites on PSD-95 and created 11 different variants to analyze how these changes affected its interactions and the formation of protein complexes.
- They discovered that phosphorylation at Ser78 reduced phase separation with GluN2B and stargazin, while phosphorylation at Ser116 promoted phase separation with stargazin, offering new insights into how PSD-95 is regulated and how it interacts within the postsynaptic density.
Article 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 GluN2B and the auxiliary protein stargazin, whereas phosphorylation of Ser116 induced phase separation with stargazin only. Thus, by genetically introducing phosphoserine site-specifically and exploring the impact on phase separation, we have provided new insights into the regulation of PSD-95 by phosphorylation and the dynamics of the PSD.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567388 | PMC |
| http://dx.doi.org/10.1016/j.isci.2021.103268 | DOI Listing |
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