Effects of microtubule (de)tyrosination on the morphology and motility of Trypanosoma brucei and cross-talk with polyglutamylation

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Thein, Marinus ; Wunderlich, Hannes ; Brehm, Lucas ; Wagner, Stella ; Weiss, Matthias ; Ersfeld, Klaus:
Effects of microtubule (de)tyrosination on the morphology and motility of Trypanosoma brucei and cross-talk with polyglutamylation.
In: Biology Open. Bd. 14 (16 Dezember 2025) Heft 12 . - bio062270.
ISSN 2046-6390
DOI: https://doi.org/10.1242/bio.062270

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Abstract

Post-translational modifications (PTMs) of microtubules control many aspects of their functionality. Specifically, the C-terminal tails of α- and β-tubulin harbour a complex array of PTMs, including polyglutamylation and the reversible detyrosination/tyrosination. The spatial proximity of these two distinct sets of PTMs suggests the possibility of a functional cross-talk between polyglutamylation and (de)tyrosination. In this study, we employ gene deletion and overexpression of the enzymes tubulin-tyrosine ligase (TTL) and tubulin-tyrosine carboxypeptidase (VASH) to provide a detailed analysis of the effects of (de)tyrosination on the protozoan parasite Trypanosoma brucei. While the deletion of either of the enzymes is not lethal, cells exhibit subtle morphological defects, resulting from both hyper- and hypotyrosination. Additionally, hypertyrosination leads to defects in motility, characterised by an increase in tumbling motion. Using the TTL and VASH deletion cells in conjunction with our previously generated trypanosomes deficient in polyglutamylation, we uncovered a cross-talk between these two PTMs. The process of microtubule detyrosination enhances polyglutamylation, which, in turn, stimulates efficient detyrosination, thus establishing a positive feedback loop between these two PTMs.