title: mGlu5 receptors regulate synaptic sumoylation via a transient PKC-dependent diffusional trapping of Ubc9 into spines.
abstract: Sumoylation plays important roles in the modulation of protein function, neurotransmission and plasticity, but the mechanisms regulating this post-translational system in neurons remain largely unknown. Here we demonstrate that the synaptic diffusion of Ubc9, the sole conjugating enzyme of the sumoylation pathway, is regulated by synaptic activity. We use restricted photobleaching/photoconversion of individual hippocampal spines to measure the diffusion properties of Ubc9 and show that it is regulated through an mGlu5R-dependent signalling pathway. Increasing synaptic activity with a GABAA receptor antagonist or directly activating mGlu5R increases the synaptic residency time of Ubc9 via a Gαq/PLC/Ca(2+)/PKC cascade. This activation promotes a transient synaptic trapping of Ubc9 through a PKC phosphorylation-dependent increase of Ubc9 recognition to phosphorylated substrates and consequently leads to the modulation of synaptic sumoylation. Our data demonstrate that Ubc9 diffusion is subject to activity-dependent regulatory processes and provide a mechanism for the dynamic changes in sumoylation occurring during synaptic transmission.
authors.affiliation: 1] University of Nice - Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 - Laboratory of Excellence 'Network for Innovation on Signal Transduction Pathways in Life Sciences', UMR7275, 660 route des lucioles, 06560 Valbonne, France [2] Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, 06560 Valbonne, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Loriol
authors.affiliation: 1] University of Nice - Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 - Laboratory of Excellence 'Network for Innovation on Signal Transduction Pathways in Life Sciences', UMR7275, 660 route des lucioles, 06560 Valbonne, France [2] Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, 06560 Valbonne, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cassé
authors.affiliation: 1] University of Nice - Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 - Laboratory of Excellence 'Network for Innovation on Signal Transduction Pathways in Life Sciences', UMR7275, 660 route des lucioles, 06560 Valbonne, France [2] Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, 06560 Valbonne, France.
authors.forename: Anouar
authors.initials: A
authors.lastname: Khayachi
authors.affiliation: 1] University of Nice - Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 - Laboratory of Excellence 'Network for Innovation on Signal Transduction Pathways in Life Sciences', UMR7275, 660 route des lucioles, 06560 Valbonne, France [2] Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, 06560 Valbonne, France.
authors.forename: Gwénola
authors.initials: G
authors.lastname: Poupon
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, 06560 Valbonne, France.
authors.forename: Magda
authors.initials: M
authors.lastname: Chafai
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, 06560 Valbonne, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Deval
authors.affiliation: 1] University of Nice - Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 - Laboratory of Excellence 'Network for Innovation on Signal Transduction Pathways in Life Sciences', UMR7275, 660 route des lucioles, 06560 Valbonne, France [2] Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, 06560 Valbonne, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Gwizdek
authors.affiliation: 1] University of Nice - Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 - Laboratory of Excellence 'Network for Innovation on Signal Transduction Pathways in Life Sciences', UMR7275, 660 route des lucioles, 06560 Valbonne, France [2] Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, 06560 Valbonne, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Martin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D013569:Synapses / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: C578936:Grm5 protein, mouse; D064529:Receptor, Metabotropic Glutamate 5; D044763:Ubiquitin-Conjugating Enzymes; D011493:Protein Kinase C; D000098843:Ubiquitin-Conjugating Enzyme UBC9