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Synapse formation and plasticity: why is phase separation required?
1School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
None:
Synapse, the most basic functional unit for neurons to communicate with each other, is highly compartmentalized. Each synapse occupies a tiny fraction of a neuron's volume but many proteins need to be targeted to and concentrated at distinct subsynaptic compartments to support neuronal communications. In presynaptic boutons, synaptic vesicles (SVs) are partitioned into several distinct functional pools via interacting with different protein condensates formed via phase separation. Protein condensates also facilitate different modes of SV release. On the postsynaptic side, neurotransmitter receptors are clustered by postsynaptic density (PSD) condensates formed by an array of scaffold proteins and regulatory enzymes. PSD condensates have unique molecular assembly modes and material properties that are directly connected to synaptic transmissions and plasticity. This brief opinion piece aims to explain why condensate formation via phase separation is essential for synapse formation and function and what unique features of protein condensates can support synaptic functions.
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