Pathophysiological Implication of Sumoylation in Intellectual Disability – SUMO-FXS

See above section

The most striking result obtained so far is the discovery of the functional consequences of FMRP sumoylation in the brain (Khayachi et al, Sumoylation regulates FMRP-mediated spinogenesis and post-synaptic maturation. Submitted to publication).

Our research aims at investigating how a defect in the regulation of FMRP sumoylation may lead to the fragile X syndrome. In the future, our work may allow to design novel therapeutic approaches to target the sumoylation system that may be deregulated in patients suffering from non-conventional forms of FXS.

Not applicable yet

Intellectual disability (ID) is the most common cause of handicap in children and represents a major economical problem worldwide. Fragile X Syndrome (FXS) is the most frequent inherited cause of ID but the mechanisms underlying the regulation of FMRP-mediated functions in the brain are still largely unknown. We discovered that FMRP is sumoylated in vivo. Sumoylation is a post-translational modification that consists in the covalent but reversible conjugation of the small protein SUMO to specific lysine residues of substrate proteins. Sumoylation regulates the fate of many proteins including several molecules involved in neurological disorders. Our project will investigate the functional consequences of FMRP sumoylation and the role of SUMO in the molecular bases of the pathophysiology of FXS. Our work will provide further insights into the mechanisms important for brain development and plasticity and into defects within these pathways that may underlie other brain disorders associated with intellectual disabilities.