Stéphane MARTIN
Chef d'équipe

 

 Chato-Astrain I. et al. (2024). Molecular Organization and Regulation of the Mammalian Synapse by the Post-Translational Modification SUMOylation. Cells

 Pronot M. et al. (2022). Bidirectional regulation of synaptic SUMOylation by Group 1 metabotropic glutamate receptors. Cell Mol Life Sci

 Pronot M. et al. (2021). Proteomic Identification of an Endogenous Synaptic SUMOylome in the Developing Rat Brain. Front Mol Neurosci

 Prieto M. et al. (2021). Missense mutation of Fmr1 results in impaired AMPAR-mediated plasticity and socio-cognitive deficits in mice. Nat Commun

 Schorova L. et al. (2019). The synaptic balance between sumoylation and desumoylation is maintained by the activation of metabotropic mGlu5 receptors. Cell Mol Life Sci

 Khayachi A. et al. (2018). Sumoylation regulates FMRP-mediated dendritic spine elimination and maturation. Nat Commun

The communication between neurons takes place in highly specialized structures called synapses. The synaptic compartment is a very dynamic area where all the molecular processes relevant to neuronal communication and plasticity are orchestrated in a spatiotemporal manner. In the past years, the post-translational modification SUMOylation has emerged as an essential regulator of neuronal communication by dynamically regulating the molecular processes at the synapse.
 
SUMOylation consists in the covalent, but reversible, enzymatic conjugation of the Small Ubiquitin-like MOdifier (SUMO1-3) polypeptides (~100 amino acids; ~11 kDa) to specific lysine residues of target proteins. More specifically, the SUMOylation/deSUMOylation balance is orchestrated by the coordinated action of the sole SUMO-conjugating enzyme Ubc9 and SUMO-deconjugating enzymes called SENPs. SUMOylation participates in the dynamic regulation of multi-protein complexes by creating new binding sites for specific interactors or alternatively, by disrupting or preventing protein-protein interactions. SUMOylation regulates the function of many proteins involved in neuronal excitability, postsynaptic differentiation as well as in synaptic communication and plasticity. A tight regulation of the SUMOylation/deSUMOylation balance is therefore critical to the brain function.
 
The overall objective of the ‘SUMOylation in neuronal function & dysfunction’ team is to decode the physiological and pathophysiological consequences of SUMOylation at the mammalian synapse. We pioneered the work on the SUMO process at the synapse and our effort over the past years clearly established that SUMOylation is developmentally and activity-dependently regulated in the brain. In the lab, we combine the use of molecular tools, advanced biochemistry and state-of-the-art live-imaging approaches to:

These data will advance our understanding of how neurons regulate the activity-dependent and synapse-specific SUMOylation of target proteins. In addition, this work provides additional insights for complementary studies on the role of SUMOylation in animal models of diseases characterized by synaptic dysfunction. In the longer term, these data will inform on strategies that may lead to tractable targets for therapeutic intervention.