CONICET PhD fellow
Director: Gaston C. Forearm
PhD Thesis Topic
Modifications of the tyrosination state of α-tubulin and microtubules by tyrosine analogues: effects on cellular functioning and their possible participation in pathologies.
Tubulin is a dimeric protein, formed by α- and β-subunits, and is the principal constituent of microtubules (MTs). As a part of the cytoskeleton, MTs are involved in different cellular functions including mitosis, cell motility, axon growth, intracellular transport and signaling, etc. Different post-translational modifications (PTMs) take place on the tubulin subunits and affect the organization of MTs and their interaction with other cellular components. The best-characterized α-tubulin modification involves the removal of the gene encoded C-terminal tyrosine residue (Tyr) by a carboxypeptidase, to expose a glutamate residue (Glu). This PTM can be reversed by an enzyme called tubulin tyrosine ligase (TTL), which reincorporates Tyr in the original position. It is also known that TTL can add other Tyr analogues, such as 3-Nitrotyrosine, L-Phenylalanine, L-Dopa and azatyrosine, instead of Tyr at the same position. The incorporation of some of these analogues could lead to the formation of MTs with altered tubulin, affecting its interaction with molecular motors and stabilizing proteins, which could affect normal cell functioning. Our aim is to study the mechanisms that relate this PTM of α-tubulin to different cellular functions and its possible participation in neuronal pathologies when TTL incorporates certain Tyr analogues.