Figure 2.

Post-synaptic regulation of the SUMO/deSUMOylation cascade at synapses by type I mGlu1/5R. (A) A short activation of mGlu5 receptors triggers a Protein Kinase C (PKC) phosphorylation-dependent trapping of the sole SUMO-conjugating enzyme Ubc9 at post-synaptic sites, leading to an increased SUMOylation and to the modulation of neuronal excitability [19]. The sustained activation of mGlu5R then leads to a decrease in the exit rate of the deSUMOylation enzyme SENP1 from dendritic spines, resulting in the post-synaptic accumulation of SENP1 to bring SUMOylation back to initial levels [26]. (B) The post-synaptic accumulation of SENP1 upon stimulation of mGlu5R involves the downstream activation of PKC or Ca²⁺/Calmodulin-dependent protein kinase II (CaMKII). Blocking mGlu1R enhances the post-synaptic accumulation of SENP1, indicating that the SUMOylation/deSUMOylation balance is bidirectionally regulated by type I mGluRs to control the levels of synaptic SUMOylation [27].