Phase separation as a mechanism for assembling dynamic postsynaptic density signalling complexes.

The postsynaptic density (PSD) is an electron dense, semi-membrane bound compartment that lies beneath postsynaptic membranes. This region is densely packed with thousands of proteins that are involved in extensive interactions. During synaptic plasticity, the PSD undergoes changes in size and composition along with changes in synaptic strength that lead to long term potentiation (LTP) or depression (LTD). It is therefore essential to understand the organization principles underlying PSD assembly and rearrangement. Here, we review exciting new findings from recent in vitro reconstitution studies and propose a hypothesis that liquid-liquid phase separation mediates PSD formation and regulation. We also discuss how the properties of PSD formed via phase separation might contribute to the biological functions observed from decades of researches. Finally, we highlight unanswered questions regarding PSD organization and how in vitro reconstitution systems may help to answer these questions in the coming years.