Alpha-Tubulin Acetylation in Trypanosoma cruzi : A Dynamic Instability of Microtubules Is Required for Replication and Cell Cycle Progression.

Autor:	Alonso VL; Laboratorio de Biología y Bioquímica de Trypanosoma cruzi, Instituto de Biología Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina.; Facultad de Ciencias Bioquimicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Rosario, Argentina., Carloni ME; Facultad de Ciencias Bioquimicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Rosario, Argentina., Gonçalves CS; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.; Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Rio de Janeiro, Brazil., Martinez Peralta G; Laboratorio de Biología y Bioquímica de Trypanosoma cruzi, Instituto de Biología Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina.; Facultad de Ciencias Bioquimicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Rosario, Argentina., Chesta ME; Facultad de Ciencias Médicas, Universidad Nacional de Rosario (UNR), Rosario, Argentina., Pezza A; Laboratorio de Biología y Bioquímica de Trypanosoma cruzi, Instituto de Biología Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina., Tavernelli LE; Laboratorio de Biología y Bioquímica de Trypanosoma cruzi, Instituto de Biología Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina., Motta MCM; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.; Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Rio de Janeiro, Brazil., Serra E; Laboratorio de Biología y Bioquímica de Trypanosoma cruzi, Instituto de Biología Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rosario, Argentina.; Facultad de Ciencias Bioquimicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Rosario, Argentina.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2021 Mar 11; Vol. 11, pp. 642271. Date of Electronic Publication: 2021 Mar 11 (Print Publication: 2021).
DOI:	10.3389/fcimb.2021.642271
Abstrakt:	Trypanosomatids have a cytoskeleton arrangement that is simpler than what is found in 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 lysine (K) 40 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 in eukaryotes. Several tubulin posttranslational modifications, including acetylation of K40, have been cataloged in trypanosomatids, but the functional importance of these modifications for microtubule dynamics and parasite biology remains largely undefined. The primary tubulin acetyltransferase was recently identified in several eukaryotes as Mec-17/ATAT, a Gcn5-related N-acetyltransferase. Here, we report that T. cruzi ATAT acetylates α-tubulin in vivo and is capable of auto-acetylation. Tc ATAT is located in the cytoskeleton and flagella of epimastigotes and colocalizes with acetylated α-tubulin in these structures. We have expressed Tc ATAT with an HA tag using the inducible vector p Tc INDEX-GW in T. cruzi . Over-expression of Tc ATAT causes increased levels of the alpha tubulin acetylated species, induces morphological and ultrastructural defects, especially in the mitochondrion, and causes a halt in the cell cycle progression of epimastigotes, which is related to an impairment of the kinetoplast division. Finally, as a result of Tc ATAT over-expression we observed that parasites became more resistant to microtubule depolymerizing drugs. These results support the idea that α-tubulin acetylation levels are finely regulated for the normal progression of T. cruzi cell cycle. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Alonso, Carloni, Gonçalves, Martinez Peralta, Chesta, Pezza, Tavernelli, Motta and Serra.)
Databáze:	MEDLINE
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