Evolutionary Divergence of Enzymatic Mechanisms for Tubulin Detyrosination
Siem van der Laan,
Maude F. Lévêque,
Guillaume Marcellin,
Lubomir Vezenkov,
Yoann Lannay,
Geronimo Dubra,
Guillaume Bompard,
Sara Ovejero,
Serge Urbach,
Andrew Burgess,
Muriel Amblard,
Yvon Sterkers,
Patrick Bastien,
Krzysztof Rogowski
Affiliations
Siem van der Laan
Tubulin Code Team, Institute of Human Genetics (IGH), CNRS-Université Montpellier, 141 rue de la Cardonille, 34293 Montpellier Cedex 5, France; Corresponding author
Maude F. Lévêque
Université Montpellier-CNRS, “MiVEGEC,” Faculté de Medicine and Centre Hospitalier Universitaire, 39 avenue Charles Flahault, 34295 Montpellier Cedex 5, France; Corresponding author
Guillaume Marcellin
Tubulin Code Team, Institute of Human Genetics (IGH), CNRS-Université Montpellier, 141 rue de la Cardonille, 34293 Montpellier Cedex 5, France
Lubomir Vezenkov
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS-Université Montpellier-ENSCM, 34093 Montpellier Cedex 5, France
Yoann Lannay
Tubulin Code Team, Institute of Human Genetics (IGH), CNRS-Université Montpellier, 141 rue de la Cardonille, 34293 Montpellier Cedex 5, France
Geronimo Dubra
Tubulin Code Team, Institute of Human Genetics (IGH), CNRS-Université Montpellier, 141 rue de la Cardonille, 34293 Montpellier Cedex 5, France
Guillaume Bompard
Tubulin Code Team, Institute of Human Genetics (IGH), CNRS-Université Montpellier, 141 rue de la Cardonille, 34293 Montpellier Cedex 5, France
Sara Ovejero
Tubulin Code Team, Institute of Human Genetics (IGH), CNRS-Université Montpellier, 141 rue de la Cardonille, 34293 Montpellier Cedex 5, France
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
Muriel Amblard
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS-Université Montpellier-ENSCM, 34093 Montpellier Cedex 5, France
Yvon Sterkers
Université Montpellier-CNRS, “MiVEGEC,” Faculté de Medicine and Centre Hospitalier Universitaire, 39 avenue Charles Flahault, 34295 Montpellier Cedex 5, France
Patrick Bastien
Université Montpellier-CNRS, “MiVEGEC,” Faculté de Medicine and Centre Hospitalier Universitaire, 39 avenue Charles Flahault, 34295 Montpellier Cedex 5, France
Krzysztof Rogowski
Tubulin Code Team, Institute of Human Genetics (IGH), CNRS-Université Montpellier, 141 rue de la Cardonille, 34293 Montpellier Cedex 5, France; Corresponding author
Summary: 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. : van der Laan et al. describe the evolutionary diversification of the VASH-mediated mechanism of tubulin detyrosination. In addition, they show that this modification plays an important role in Trypanosoma parasites, where it regulates cell division and cell morphology. Keywords: detyrosination, cell cycle, activator, peptide, inhibitor, parasite, tubulin, modification, vash, microtubule