Alpha-tubulin acetylation in Trypanosoma cruzi

VICTORIA ALONSO; GONZALO MARTINEZ PERALTA; PAMELA CRIBB

Rosario

Otro; Instruct Theoretical and Practical Course: Integrative Structural Biology in Latin America; 2020

IBR

The cytoskeleton of trypanosomatids has a simpler arrange than most eukaryotic cells. However, it is precisely organized and constituted by stable microtubules. Such microtubules compose the mitotic spindle during mitosis, the basal body, the flagellar axoneme and the subpellicular microtubules, which are connected to each other and also to the plasma membrane forming a helical arrangement along the central axis of the parasite cell body. Subpellicular, mitotic and axonemal microtubules are extensively acetylated in Trypanosoma cruzi. Acetylation on K40 of α-tubulin is conserved from lower eukaryotes to mammals and is associated with microtubule stability. It is also known that K40 acetylation occurs significantly on flagella, centrioles, cilia, basal body and the mitotic spindle. Several tubulin posttranslational modifications, including acetylation of K40, have been catalogued in trypanosomatids, but the functional importance of these modifications for microtubule dynamics and parasite biology remains largely undefined. The primary tubulin acetyltransferase that delivers this modification was recently identified in several eukaryotes as Mec-17/ATAT, a Gcn5-related N-acetyltransferase.Our reaserch group have identified and characterized the acetyltransferase responsible for mediating K40 α-tubulin acetylation in T. cruzi (TcαTAT). TcαTAT overexpression conduces to a hyperacetylation of a-tubulin that severely affects the normal progression of the cell cycle in epimastigotes. Furthermore, the overexpression of TcαTAT generates a defect in cytokinesis and the appearance of an atypical structure near the kinetoplast.