The synaptic balance between sumoylation and desumoylation is maintained by the activation of metabotropic mGlu5 receptors
- Others:
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- We gratefully acknowledge the 'Agence Nationale de la Recherche (Fr)' (ANR-15-CE16-0015-01) and the Bettencourt-Schueller foundation for financial support.
- ANR-15-CE16-0015,SUMO-FXS,Implication physiopathologique de la sumoylation dans la déficience intellectuelle(2015)
- ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015)
Description
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.
Abstract
International audience
Additional details
- URL
- https://www.hal.inserm.fr/inserm-02474777
- URN
- urn:oai:HAL:inserm-02474777v1
- Origin repository
- UNICA