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

• DOI: 10.1007/s00018-019-03075-8
• Publication Date: 2019-03-23T11:02:26Z
• Authors: Lenka Schorova; Marie Pronot; Gwénola Poupon; Marta Prieto; Alessandra Folci; Anouar Khayachi; Frédéric Brau; Frédéric Cassé; Carole Gwizdek; Stéphane Martin
• Keywords: [SDV]Life Sciences [q-bio]; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology; Receptor, Metabotropic Glutamate 5; SUMO-1 Protein; [SDV.BC]Life Sciences [q-bio]/Cellular Biology; Desumoylation; 03 medical and health sciences; SENP1; Chlorocebus aethiops; Animals; Humans; Rats, Wistar; Cells, Cultured; Neurons; 0303 health sciences; Sumoylation; Synapse; 3. Good health; Cysteine Endopeptidases; mGlu5 receptor; Microscopy, Fluorescence; COS Cells; Synapses; Ubiquitin-Conjugating Enzymes; [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; Fluorescence Recovery After Photobleaching

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.