The synaptic balance between sumoylation and desumoylation is maintained by the activation of metabotropic mGlu5 receptors

• Published in: Cellular and molecular life sciences : CMLS 2019-08, Vol.76 (15), p.3019-3031
• Main Authors: Schorova, Lenka, Pronot, Marie, Poupon, Gwénola, Prieto, Marta, Folci, Alessandra, Khayachi, Anouar, Brau, Frédéric, Cassé, Frédéric, Gwizdek, Carole, Martin, Stéphane
• Format: Article
• Language: English
• Subjects: Activation; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; Cell Biology; Cells, Cultured; Cellular Biology; Chlorocebus aethiops; COS Cells; Cysteine Endopeptidases - metabolism; Dendritic spines; Enzymes; Fluorescence Recovery After Photobleaching; Glutamic acid receptors (metabotropic); Hippocampus; Homeostasis; Humans; Life Sciences; Microscopy, Fluorescence; Neurological diseases; Neuromodulation; Neurons - cytology; Neurons - metabolism; Neurotransmitter release; Original; Original Article; Photobleaching; Post-translation; Rats, Wistar; Receptor, Metabotropic Glutamate 5 - metabolism; Receptors; SUMO protein; SUMO-1 Protein - metabolism; Sumoylation; Synapses; Synapses - metabolism; Synaptic plasticity; Time dependence; Ubiquitin-Conjugating Enzymes - metabolism
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-019-03075-8

Sumoylation is a reversible post-translational modification essential to the modulation of neuronal function, including neurotransmitter release and synaptic plasticity. A tightly regulated equilibrium between the sumoylation and desumoylation processes is critical to the brain function and its disruption has been associated with several neurological disorders. This sumoylation/desumoylation balance is governed by the activity of the sole SUMO-conjugating enzyme Ubc9 and a group of desumoylases called SENPs, respectively. We previously demonstrated that the activation of type 5 metabotropic glutamate receptors (mGlu5R) triggers the transient trapping of Ubc9 in dendritic spines, leading to a rapid increase in the overall synaptic sumoylation. However, the mechanisms balancing this increased synaptic sumoylation are still not known. Here, we examined the diffusion properties of the SENP1 enzyme using a combination of advanced biochemical approaches and restricted photobleaching/photoconversion of individual hippocampal spines. We demonstrated that the activation of mGlu5R leads to a time-dependent decrease in the exit rate of SENP1 from dendritic spines. The resulting post-synaptic accumulation of SENP1 restores synaptic sumoylation to initial levels. Altogether, our findings reveal the mGlu5R system as a central activity-dependent mechanism to maintaining the homeostasis of sumoylation at the mammalian synapse.