At neuronal synapses, several dense structures coexist similar to the way oil and water stay as two immiscible liquids. It has been considered that phase separation drives the formation of these dense structures composed of numerous structural and functional proteins. However, the mechanism by which multi-component phase separation is regulated in cells remains elusive. Researchers led by Yongdae Shin, Seoul National University, South Korea, examined protein components at inhibitory synapses to uncover how a combination of intra- and intermolecular interactions can give rise to the regulated assembly of macromolecule-rich structures, also called biomolecular condensates. They found that the phase separation behavior of gephyrin, a key inhibitory synapse scaffold, is largely modulated by the presence of other inhibitory synapse components. This study highlights how the physics of biomolecular phase separation can facilitate the localized organization of functional assemblies, and ultimately reliable neuronal information flow.

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