There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
The postsynaptic density (PSD) at inhibitory synapses is a complex molecular assembly
that serves as a platform for the interaction of neurotransmitter receptors, scaffold
and adapter proteins, cytoskeletal elements and signalling molecules. The stability
of the PSD depends on a multiplicity of interactions linking individual components.
At the same time the PSD retains a substantial degree of flexibility. The continuous
exchange of synaptic molecules and the preferential addition or removal of certain
components induce plastic changes in the synaptic structure. This property necessarily
implies that interactors are in dynamic equilibrium and that not all synaptic binding
sites are occupied simultaneously. This review discusses the molecular plasticity
of inhibitory synapses in terms of the connectivity of their components. Whereas stable
protein complexes are marked by stoichiometric relationships between subunits, the
majority of synaptic interactions have fractional occupancy, which is here defined
as the non-saturation of synaptic binding sites. Fractional occupancy can have several
causes: reduced kinetic or thermodynamic stability of the interactions, an imbalance
in the concentrations or limited spatio-temporal overlap of interacting proteins,
negative cooperativity or mutually exclusive binding. The role of fractional occupancy
in the regulation of synaptic structure and function is explored based on recent data
about the connectivity of inhibitory receptors and scaffold proteins. I propose that
the absolute quantification of interactors and their stoichiometry at identified synapses
can provide new mechanistic insights into the dynamic properties of inhibitory PSDs
at the molecular level. This article is part of the special issue entitled 'Mobility
and trafficking of neuronal membrane proteins'.