FAM81A is a postsynaptic protein that regulates the condensation of postsynaptic proteins via liquid-liquid phase separation

Takeshi Kaizuka, Taisei Hirouchi, Takeo Saneyoshi, Toshihiko Shirafuji, Mark O Collins, Seth G N Grant, Yasunori Hayashi, Toru Takumi

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Proteome analyses of the postsynaptic density (PSD), a proteinaceous specialization beneath the postsynaptic membrane of excitatory synapses, have identified several thousands of proteins. While proteins with predictable functions have been well studied, functionally uncharacterized proteins are mostly overlooked. In this study, we conducted a comprehensive meta-analysis of 35 PSD proteome datasets, encompassing a total of 5,869 proteins. Employing a ranking methodology, we identified 97 proteins that remain inadequately characterized. From this selection, we focused our detailed analysis on the highest-ranked protein, FAM81A. FAM81A interacts with PSD proteins, including PSD-95, SynGAP, and NMDA receptors, and promotes liquid-liquid phase separation of those proteins in cultured cells or in vitro. Down-regulation of FAM81A in cultured neurons causes a decrease in the size of PSD-95 puncta and the frequency of neuronal firing. Our findings suggest that FAM81A plays a crucial role in facilitating the interaction and assembly of proteins within the PSD, and its presence is important for maintaining normal synaptic function. Additionally, our methodology underscores the necessity for further characterization of numerous synaptic proteins that still lack comprehensive understanding.

Original languageEnglish
Pages (from-to)e3002006
JournalPLoS Biology
Volume22
Issue number3
DOIs
Publication statusPublished - 7 Mar 2024

Keywords / Materials (for Non-textual outputs)

  • Proteome/metabolism
  • Phase Separation
  • Disks Large Homolog 4 Protein/metabolism
  • Synapses/metabolism
  • Synaptic Membranes

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