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

Abstract : 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.
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Submitted on : Tuesday, February 11, 2020 - 3:57:50 PM
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Lenka Schorova, Marie Pronot, Gwenola Poupon, Marta Prieto, Alessandra Folci, et al.. The synaptic balance between sumoylation and desumoylation is maintained by the activation of metabotropic mGlu5 receptors. Cellular and Molecular Life Sciences, Springer Verlag, 2019, 76 (15), pp.3019-3031. ⟨10.1007/s00018-019-03075-8⟩. ⟨inserm-02474777⟩



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