Regulation of AMPA receptor surface diffusion by PSD-95 slots

Excitatory synaptic transmission is largely mediated by AMPA receptors (AMPARs) present at the postsynaptic density. Recent studies in single molecule tracking of AMPAR has revealed that extrasynaptic AMPARs are highly mobile and thus might serve as a readily available pool for their synaptic recruitment during synaptic plasticity events such as long-term potentiation (LTP). Because this hypothesis relies on the cell's ability to increase the number of diffusional traps or 'slots' at synapses during LTP, we will review a number of protein-protein interactions that might impact AMPARs lateral diffusion and thus potentially serve as slots. Recent studies have identified the interaction between the AMPAR-Stargazin complex and PSD-95 as the minimal components of the diffusional trapping slot. We will overview the molecular basis of this critical interaction, its activity-dependent regulation and its potential contribution to LTP.

► AMPA receptors diffuse in neuronal membranes and are reversibly trapped at synapses. ► AMPAR-Stargazin complex interaction with PSD-95 traps AMPAR at synapses. ► Anchoring of TARP-containing AMPARs involves multivalent PDZ domain interactions. ► Stargazin phosphorylation regulates AMPAR diffusion by regulating binding to PSD-95.