The organisation and turnover of synaptic proteins within molecular supercomplexes

Abstract

AbstractPost Synaptic Density 95 (PSD95) is an important scaffolding protein found in the postsynaptic terminal of vertebrate excitatory synapses. PSD95 is required to structurally organize over 80 proteins, including glutamate receptors, signaling, adhesion and other molecules, into ∼1.5 MDa supercomplexes within the post-synaptic density. Despite its importance, little is known about the dynamics or heterogeneity of PSD95 in such supercomplexes. We have used single-molecule and super-resolution microscopy to probe the molecular organization of individual PSD95-containing supercomplexes isolated from mouse brain, revealing the number of PSD95 copies in each supercomplex, and the distances between the individual proteins. We have also examined the dynamic nature of these supercomplexes, discovering that PSD95 is replaced over several days. Importantly, we found that old copies of PSD95 are replaced with new protein within the supercomplexes, independent of whole-supercomplex turnover. This finding suggests the existence of a mechanism that allows for the maintenance of the overall structure of the post-synaptic density, despite the rapid turnover of individual proteins.