Physiology and pathophysiology of brain SUMOylation

Présentation

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 in the mammalian brain. 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:

1. Decipher the molecular mechanisms driving the regulation of the activity-dependent SUMOylation / deSUMOylation balance at synapses.
2. Identify and characterize the synaptic network of SUMOylated proteins.
3. Define the physiological role of selected SUMOylated proteins important for the brain function, and investigate how disruption or alteration of their SUMOylation can participate in the etiology of brain disorders.

Alumni

• Post-doctoral fellows
  • Marie PRONOT (2021-2022) -> Post-doc – CDBS – Edinburgh – Scotland
  • Alessandra FOLCI (2017-2019) -> Permanent researcher – CNR – Milan – Italy
  • Frédéric CASSE (2012-2015) -> Permanent IR/engineer – Biotargen – Caen – Fr
  • Céline LORIOL (2009-2011)

• PhD students
  • Félicie KIEFFER (2019-2022)
  • Marie PRONOT (2017-2021) -> Post-doc – IPMC – Fr
  • Marta PRIETO (2016-2020) -> Post-doc – GIN – Grenoble – Fr
  • Lenka SCHOROVA (2014-2018) -> Research Program Manager – Montreal – Canada
  • Anouar KHAYACHI (2011-2015) -> Post-doc – MNI – Montreal – Canada