Tubulin modifying enzymes as target for the treatment of tau-related diseases
Krzysztof Rogowski, Khaled Hached, Carole Crozet, Siem Van Der Laan
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.
Krzysztof Rogowski, Khaled Hached, Carole Crozet, Siem Van Der Laan
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
Bompard G, van Dijk J, Cau J, Marcellin G, Lannay Y, Lawera A, van der Laan S and Rogowski K.
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.
Devambez I, van Dijk J, Benlefki S, Layalle S, Grau Y, Rogowski K, Parmentier ML, Soustelle L.
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
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