New alpha-tubulin processing enzymes acting in Drosophila germlines – DetyrGerm

Detyrosination is a post-translational modification associated with stable microtubules, which consists in the removal of the last amino acid from the C-terminus of alpha-tubulin. Up to now, two families of detyrosinases have been identified in mammalian cells. Nevertheless, these families are not conserved in Drosophila where detyrosination takes place specifically in the male germline. Through a genetic screen we recently identified a third class of detyrosinase acting during fly spermatogenesis. The first part of this project aims at characterizing the function of this enzyme and the role of detyrosination in the male germline. Strikingly, we provide strong evidence that a female-specific isotype of aplha-tubulin, which carries a terminal phenylalanine, is similarly processed in the female germline, by another enzyme. Based on our recent discovery of the new detyrosinase TMCP1 in mammals (Nicot et al. Sci Adv 2023) and of a new detyrosinase in Drosophila, we propose in a second part a strategy to identify this unknown “dephenylalaninase” and analyze its function. This project will therefore lead to the characterization of two new families of aplha-tubulin carboxy-peptidases and paves the way for the identification of their putative functional homologs in mammals.