Synaptic Vesicle Clusters at Synapses: A Distinct Liquid Phase?

Phase separation in the cytoplasm is emerging as a major principle in intracellular organization. In this process, sets of macromolecules assemble themselves into liquid compartments that are distinct from the surrounding medium but are not delimited by membrane boundaries. Here, we discuss how phase separation, in which a component of one of the two phases is vesicles rather than macromolecules, could underlie the formation of synaptic vesicle (SV) clusters in proximity to presynaptic sites. The organization of SVs into a liquid phase could explain how SVs remain tightly clustered without being stably bound to a scaffold so that they can be efficiently recruited to release site by active zone components.