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

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Postsynaptic densities (PSDs) are crucial protein-rich compartments regulating synaptic plasticity.
• Understanding PSD formation and dynamics is key to neuroscience.
• SynGAP is a key abundant protein within PSDs involved in regulating synaptic function.

Purpose of the Study:

• To investigate the molecular mechanism of SynGAP anchoring within postsynaptic densities.
• To elucidate the role of SynGAP-PSD-95 interactions in PSD formation and dynamics.
• To explore the contribution of phase separation to PSD structure and function.

Main Methods:

• Biochemical assays to determine SynGAP oligomerization state.
• Co-immunoprecipitation to study SynGAP-PSD-95 binding.
• In vitro phase separation assays to observe droplet formation.
• Confocal microscopy to visualize SynGAP dynamics in relation to PSDs.

Main Results:

• SynGAP forms a homo-trimer and binds multivalent PSD-95 proteins.
• The SynGAP-PSD-95 complex undergoes liquid-liquid phase separation, forming droplets similar to PSDs.
• This multivalent interaction is essential for SynGAP anchoring and activity-dependent dispersion from PSDs.

Conclusions:

• A novel mechanism for SynGAP dynamic anchoring at PSDs via multivalent interactions and phase separation is proposed.
• Phase separation is suggested as a key mechanism for the formation of postsynaptic densities.
• This study provides insights into the molecular basis of synaptic plasticity and PSD organization.