title: Phase Transition in Postsynaptic Densities Underlies Formation of Synaptic Complexes and Synaptic Plasticity.
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.
authors: Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors: Menglong
authors: M
authors: Zeng
authors: Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors: Yuan
authors: Y
authors: Shang
authors: Department of Neuroscience and Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Yoichi
authors: Y
authors: Araki
authors: Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors: Tingfeng
authors: T
authors: Guo
authors: Department of Neuroscience and Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Richard L
authors: RL
authors: Huganir
authors: Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address: mzhang@ust.hk.
authors: Mingjie
authors: M
authors: Zhang
mesh_terms: D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D057809:HEK293 Cells; D006367:HeLa Cells; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D044367:Phase Transition; D057907:Post-Synaptic Density / Q000378:metabolism*; D000072756:Protein Conformation, alpha-Helical; D055503:Protein Multimerization; D051381:Rats; D020703:ras GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C484739:SYNGAP1 protein, human; D020703:ras GTPase-Activating Proteins