Presynaptic bouton compartmentalization and postsynaptic density-mediated glutamate receptor clustering via phase separation

Neuronal synapses encompass three compartments: presynaptic axon terminal, synaptic cleft, and postsynaptic dendrite. Each compartment contains densely packed molecular machineries that are involved in synaptic transmission. In recent years, emerging evidence indicates that the assembly of these membraneless substructures or assemblies that are not enclosed by membranes are driven by liquid-liquid phase separation. We review here recent studies that suggest the phase separation-mediated organization of these synaptic compartments. We discuss how synaptic function may be linked to its organization as biomolecular condensates. We conclude with a discussion of areas of future interest in the field for better understanding of the structural architecture of neuronal synapses and its contribution to synaptic functions.This article is part of the Neuropharmacology Special Issue on ‘Glutamate Receptors - The Glutamatergic Synapse’.