Tubulin modifying enzymes as target for the treatment of tau-related diseases
Krzysztof Rogowski, Khaled Hached, Carole Crozet, Siem Van Der Laan
Tubulin code
Génétique, biologie cellulaire et développement
Microtubules (MTs) are essential cytoskeletal elements composed of alpha- and beta-Tubulin heterodimers. They are involved in a range of cellular functions including cell division, maintenance of cell shape, intracellular transport as well as cell motility.
The mechanisms that allow MTs to perform such a diverse range of functions are poorly understood, but it is clear that each specific MT function requires the recruitment of a particular set of MT-associated proteins (MAPs). Strikingly, many MAPs interact with the C-terminal tails of Tubulins, which are known to protrude from the MT surface and to undergo several unusual post-translational modifications (Westermann and Weber, 2003).
Such Tubulin C-terminal modifications include the removal of the very C-terminal tyrosine from alpha-Tubulin and two so-called poly-modifications, namely poly-glutamylation and poly-glycylation, which consist in the addition of side chains of either glutamate or glycine residues to the C-terminal tails of both alpha- and beta-Tubulin.
The combination of the different Tubulin C-terminal modifications together with the fact that the side chains generated by the poly-modifications vary in length provides a high potential for encoding patterns on the MT surface that might recruit specific MAPs and allow the functional adaptation of MTs.
In addition, since all these modifications have been shown to be reversible, they permit rapid changes in the MT properties.
PUBLICATIONS DE L'ÉQUIPE
Evolutionary Divergence of Enzymatic Mechanisms for Tubulin Detyrosination.
van der Laan S, Lévêque MF, Marcellin G, Vezenkov L, Lannay Y, Dubra G, Bompard G, Ovejero S, Urbach S, Burgess A, Amblard M, Sterkers Y, Bastien P, Rogowski K
CSAP acts as a regulator of TTLL-mediated microtubule glutamylation
Bompard G, van Dijk J, Cau J, Marcellin G, Lannay Y, Lawera A, van der Laan S and Rogowski K.
Vasohibins/SVBP are tubulin carboxypeptidases (TCP) that regulate neuron differentiation
Aillaud, C., Bosc, C., Peris, L., Bosson, A., Heemeryck, P.,Van Dijk, J., Le Friec, J., Boulan, B., Vossier, F., Sanman, L.E., Syed, S., Amara, N., Couté, Y., Lafanechère, L., Denarier, E., Delphin, C., Pelletier, L., Humbert, S., Bogyo, M., Andrieux*, A., Rogowski*, K., Moutin*, M.J.
Identification of DmTTLL5 as a Major Tubulin Glutamylase in the Drosophila Nervous System
Devambez I, van Dijk J, Benlefki S, Layalle S, Grau Y, Rogowski K, Parmentier ML, Soustelle L.
PUBLICATIONS COMMUNES
Evolutionary Divergence of Enzymatic Mechanisms for Tubulin Detyrosination.
van der Laan S, Lévêque MF, Marcellin G, Vezenkov L, Lannay Y, Dubra G, Bompard G, Ovejero S, Urbach S, Burgess A, Amblard M, Sterkers Y, Bastien P, Rogowski K
2019 - Cell Rep
, 29(12):4159-4171.e6 31851940 
Service porteur :
Tubulin code
Microtubule polyglutamylation and acetylation drive microtubule dynamics critical for platelet formation.
van Dijk J, Bompard G, Cau J, Kunishima S, Rabeharivelo G, Mateos-Langerak J, Cazevieille C, Cavelier P, Boizet-Bonhoure B, Delsert C, Morin N
2018 - BMC Biol
, 16(1):116 30336771
Service porteur :
Développement et Pathologie de la Gonade
