Phase Transition in Postsynaptic Densities Underlies Formation of Synaptic Complexes and Synaptic Plasticity

Menglong Zeng, Yuan Shang, Yoichi Araki, Tingfeng Guo, Richard L. Huganir, Mingjie Zhang

Research output: Contribution to journalArticle

Abstract

Postsynaptic densities (PSDs) are membrane semi-enclosed, submicron protein-enriched cellular compartments beneath postsynaptic membranes, which constantly exchange their components with bulk aqueous cytoplasm in synaptic spines. Formation and activity-dependent modulation of PSDs is considered as one of the most basic molecular events governing synaptic plasticity in the nervous system. In this study, we discover that SynGAP, one of the most abundant PSD proteins and a Ras/Rap GTPase activator, forms a homo-trimer and binds to multiple copies of PSD-95. Binding of SynGAP to PSD-95 induces phase separation of the complex, forming highly concentrated liquid-like droplets reminiscent of the PSD. The multivalent nature of the SynGAP/PSD-95 complex is critical for the phase separation to occur and for proper activity-dependent SynGAP dispersions from the PSD. In addition to revealing a dynamic anchoring mechanism of SynGAP at the PSD, our results also suggest a model for phase-transition-mediated formation of PSD.

Original languageEnglish (US)
Pages (from-to)1163-1175.e12
JournalCell
Volume166
Issue number5
DOIs
StatePublished - Aug 25 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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