Activity-dependent regulation of the sumoylation machinery in rat hippocampal neurons

Abstract

Background information: Sumoylation is a key post-translational modification by which the Small Ubiquitin-like MOdifier (SUMO) polypeptide is covalently attached to specific lysine residues of substrate proteins through a specific enzymatic pathway. Although sumoylation participates in the regulation of nuclear homeostasis, the sumoylation machinery is also expressed outside of the nucleus where little is still known regarding its non-nuclear functions, particularly in the Central Nervous System (CNS). We recently reported that the sumoylation process is developmentally regulated in the rat CNS. Results: Here, we demonstrate that there is an activity-dependent redistribution of endogenous sumoylation enzymes in hippocampal neurons. By performing biochemical and immunocytochemical experiments on primary cultures of rat hippocampal neurons, we show that sumoylation and desumoylation enzymes are differentially redistributed in and out of synapses upon neuronal stimulation. This enzymatic redistribution in response to a neuronal depolarisation results in the transient decrease of sumoylated protein substrates at synapses. Conclusions: Taken together, our data identify an activity-dependent regulation of the sumoylation machinery in neurons that directly impacts on synaptic sumoylation levels. This process may provide a mechanism for neurons to adapt their physiological responses to changes occurring during neuronal activation. Sumoylation is a post-translational modification shown to be central to the regulation of nuclear homeostasis but little is known regarding its role outside of the nucleus, particularly at synapses. Here, we show that there is a differential synaptic redistribution of the sumoylation machinery following neuronal depolarisation. We find that this reorganisation directly impacts on synaptic sumoylation levels, indicating that the sumoylation machinery is dynamically regulated upon neuronal activity to participate to synaptic regulatoryfunctions. Copyright © 2013 Soçiété Française des Microscopies and Soçiété de Biologie Cellulaire de France.