Bidirectional regulation of synaptic SUMOylation by Group 1 metabotropic glutamate receptors.

Autor: Pronot M; Université Côte d'Azur, CNRS, IPMC, Valbonne, France., Poupon G; Université Côte d'Azur, CNRS, IPMC, Valbonne, France., Pizzamiglio L; Université Côte d'Azur, CNRS, IPMC, Valbonne, France., Prieto M; Université Côte d'Azur, CNRS, IPMC, Valbonne, France., Chato-Astrain I; Université Côte d'Azur, CNRS, IPMC, Valbonne, France., Lacagne I; Université Côte d'Azur, CNRS, IPMC, Valbonne, France., Schorova L; Université Côte d'Azur, CNRS, IPMC, Valbonne, France., Folci A; Université Côte d'Azur, CNRS, IPMC, Valbonne, France., Brau F; Université Côte d'Azur, CNRS, IPMC, Valbonne, France., Martin S; Université Côte d'Azur, INSERM, CNRS, IPMC, Valbonne, France. martin@ipmc.cnrs.fr.; Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, Centre National de la Recherche Scientifique, Université Côte d'Azur, 660 route des lucioles, 06560, Valbonne, France. martin@ipmc.cnrs.fr.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2022 Jun 23; Vol. 79 (7), pp. 378. Date of Electronic Publication: 2022 Jun 23.
DOI: 10.1007/s00018-022-04405-z
Abstrakt: SUMOylation is a post-translational modification essential to cell homeostasis. A tightly controlled equilibrium between SUMOylation and deSUMOylation processes is also critical to the neuronal function including neurotransmitter release and synaptic transmission and plasticity. Disruption of the SUMOylation homeostasis in neurons is associated with several neurological disorders. The balance between the SUMOylation and deSUMOylation of substrate proteins is maintained by a group of deSUMOylation enzymes called SENPs. We previously showed that the activation of type 5 metabotropic glutamate receptors (mGlu5R) first triggers a rapid increase in synaptic SUMOylation and then upon the sustained activation of these receptors, the deSUMOylase activity of SENP1 allows the increased synaptic SUMOylation to get back to basal levels. Here, we combined the use of pharmacological tools with subcellular fractionation and live-cell imaging of individual hippocampal dendritic spines to demonstrate that the synaptic accumulation of the deSUMOylation enzyme SENP1 is bidirectionally controlled by the activation of type 1 mGlu1 and mGlu5 receptors. Indeed, the pharmacological blockade of mGlu1R activation during type 1 mGluR stimulation leads to a faster and greater accumulation of SENP1 at synapses indicating that mGlu1R acts as a brake to the mGlu5R-dependent deSUMOylation process at the post-synapse. Altogether, our findings reveal that type 1 mGluRs work in opposition to dynamically tune the homeostasis of SUMOylation at the mammalian synapse.
(© 2022. The Author(s).)
Databáze: MEDLINE
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