mGlu5 receptors regulate synaptic sumoylation via a transient PKC-dependent diffusional trapping of Ubc9 into spines

Céline Loriol, Frédéric Cassé, Anouar Khayachi, Gwénola Poupon, Magda Chafai, Emmanuel Deval, Carole Gwizdek and Stéphane Martin ()
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Céline Loriol: 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
Frédéric Cassé: 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
Anouar Khayachi: 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
Gwénola Poupon: 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
Magda Chafai: Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275
Emmanuel Deval: Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275
Carole Gwizdek: 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
Stéphane Martin: 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

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: 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/Ca2+/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.

Date: 2014
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DOI: 10.1038/ncomms6113

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