Finding functions of phase separation in the presynapse. (August 2021) - McDonald, Nathan A.
Abstract: Synapses are the basic units of neuronal communication. Understanding how synapses assemble and function is therefore essential to understanding nervous systems. Decades of study have identified many molecular components and functional mechanisms of synapses. Recently, an additional level of synaptic protein organization has been identified: phase separation. In the presynapse, components of the central active zone and a synaptic vesicle-clustering factor have been shown to form liquid–liquid phase-separated condensates or hydrogels. New in vivo functional studies have directly tested how phase separation impacts both synapse formation and function. Here, we review this emerging evidence for in vivo functional roles of phase separation at the presynapse and discuss future functional studies necessary to understand its complexity. Highlights: Multiple components of neuronal presynapses are capable of phase separation in vitro . In vivo studies show presynaptic phase separation is critical for active zone assembly. Many aspects of presynaptic phase separation require functional testing. Phase separation–specific loss-of-function mutants can test in vivo functions.