SUMOylation, Arc and the regulation homeostatic synaptic scaling: Implications in health and disease

Neurons compensate for changes in network activity by altering the sensitivity of transmission across collections of synapses by up- or downregulating the number of synaptic AMPA receptors. We recently reported that, in parallel to increasing AMPA receptor surface expression, suppression of network activity with TTX increases protein SUMOylation by decreasing levels of the deSUMOylating enzyme SENP1. SUMOylation of the immediate early gene product Arc is required for synaptic scaling. These results reveal a previously unsuspected role for protein SUMOylation in activity-dependent AMPA receptor trafficking and the regulation of neuronal network activity, processes which play important roles in neurodegenerative disease.