Activity-dependent regulation of the sumoylation machinery in rat hippocampal neurons.
BACKGROUND
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.
Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR-7275, University of Nice Sophia-Antipolis, Valbonne 06560, France.
Céline
C
Loriol
Anouar
A
Khayachi
Gwénola
G
Poupon
Carole
C
Gwizdek
Stéphane
S
Martin
D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D013569:Synapses / Q000378:metabolism
D025841:Small Ubiquitin-Related Modifier Proteins