Ubiquitination consists in the attachment of ubiquitin (Ub) to target proteins. This post-translational modification controls the fate of proteins (via proteasomal or lysosomal mechanisms) and is imperative in the regulation of various key cellular processes such as endocytosis, subcellular localization and activity of proteins. Ubiquitination can be reversed by deubiquitinating enzymes (DUBs), a class of proteases that regulate degradative processes and contribute to the recycling of Ub molecules. Deregulation of the Ub conjugation/deconjugation system has been linked to the pathogenesis of various human diseases like cancers and neurodegenerative disorders. It is now clear that maintaining a balanced interplay between ubiquitinating and deubiquitinating reactions is of crucial pathophysiological importance for the brain.
The project aims at charactering the effects of brain deubiquitinating enzymes on the activity and trafficking of selected neuronal Ca²⁺ channels. The thesis should also explore the involvement of the Ub conjugation/deconjugation system in the control of intracellular Ca²⁺ stores. The work will be done in collaboration with the group of Prof C. Meyer-Schwesinger (Hamburg, Germany).

Keywords
Neuronal calcium channels, calcium signalling, ubiquitination, neuronal physiology, intracellular trafficking.

PhD supervisor