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Cell Rep. 2019 Dec 17;29(12):4159-4171.e6. doi: 10.1016/j.celrep.2019.11.074.

Evolutionary Divergence of Enzymatic Mechanisms for Tubulin Detyrosination.

Author information

1
Tubulin Code Team, Institute of Human Genetics (IGH), CNRS-Université Montpellier, 141 rue de la Cardonille, 34293 Montpellier Cedex 5, France. Electronic address: siem.vanderlaan@igh.cnrs.fr.
2
Université Montpellier-CNRS, "MiVEGEC," Faculté de Medicine and Centre Hospitalier Universitaire, 39 avenue Charles Flahault, 34295 Montpellier Cedex 5, France. Electronic address: maude.leveque@umontpellier.fr.
3
Tubulin Code Team, Institute of Human Genetics (IGH), CNRS-Université Montpellier, 141 rue de la Cardonille, 34293 Montpellier Cedex 5, France.
4
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS-Université Montpellier-ENSCM, 34093 Montpellier Cedex 5, France.
5
Functional Proteomics Platform (FPP), IGF, Université Montpellier, CNRS, INSERM, Montpellier, France.
6
ANZAC Research Institute, Gate 3 Hospital Rd., Concord, Sydney, NSW 2139, Australia; The University of Sydney Concord Clinical School, Faculty of Medicine and Health, Sydney, NSW, Australia.
7
Université Montpellier-CNRS, "MiVEGEC," Faculté de Medicine and Centre Hospitalier Universitaire, 39 avenue Charles Flahault, 34295 Montpellier Cedex 5, France.
8
Tubulin Code Team, Institute of Human Genetics (IGH), CNRS-Université Montpellier, 141 rue de la Cardonille, 34293 Montpellier Cedex 5, France. Electronic address: krzysztof.rogowski@igh.cnrs.fr.

Abstract

The two related members of the vasohibin family, VASH1 and VASH2, encode human tubulin detyrosinases. Here we demonstrate that, in contrast to VASH1, which requires binding of small vasohibin binding protein (SVBP), VASH2 has autonomous tubulin detyrosinating activity. Moreover, we demonstrate that SVBP acts as a bona fide activator of both enzymes. Phylogenetic analysis of the vasohibin family revealed that regulatory diversification of VASH-mediated tubulin detyrosination coincided with early vertebrate evolution. Thus, as a model organism for functional analysis, we used Trypanosoma brucei (Tb), an evolutionarily early-branched eukaryote that possesses a single VASH and encodes a terminal tyrosine on both α- and β-tubulin tails, both subject to removal. Remarkably, although detyrosination levels are high in the flagellum, TbVASH knockout parasites did not present any noticeable flagellar abnormalities. In contrast, we observed reduced proliferation associated with profound morphological and mitotic defects, underscoring the importance of tubulin detyrosination in cell division.

KEYWORDS:

activator; cell cycle; detyrosination; inhibitor; microtubule; modification; parasite; peptide; tubulin; vash

PMID:
31851940
DOI:
10.1016/j.celrep.2019.11.074
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