Evolutionary Divergence of Enzymatic Mechanisms for Tubulin Detyrosination

Siem van Der Laan (1) , Maude Lévêque (2) , Guillaume Marcellin (1) , Lubomir Vezenkov (3) , Yoann Lannay (1) , Geronimo Dubra , Guillaume Bompard (1) , Sara Ovejero (1) , Serge Urbach (4) , Andrew Burgess (5) , Muriel Amblard (3) , Yvon Sterkers (2) , Patrick Bastien (6, 2) , Krzysztof Rogowski (4)

1 IGH - Institut de génétique humaine
2 MIVEGEC-BioGEPPE - Biologie, Génétique et Pathologie des Pathogènes Eucaryotes
3 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
4 IGF - Institut de Génomique Fonctionnelle
5 Garvan Institute of medical research
6 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]

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 a- and b-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.

Domaines: Organisation et fonctions cellulaires [q-bio.SC]; Biologie structurale [q-bio.BM]

Siem van Der Laan, Maude Lévêque, Guillaume Marcellin, Lubomir Vezenkov, Yoann Lannay, et al.. Evolutionary Divergence of Enzymatic Mechanisms for Tubulin Detyrosination. Cell Reports, 2019, 29 (12), pp.4159 - 4171. ⟨10.1016/j.celrep.2019.11.074⟩. ⟨hal-03080532⟩