Régulation de la dynamique des microtubules et de leurs fonctions

Leader

Research center

26 rue d'Ulm
75005 Paris
Geneviève Almouzni

Institution

CNRS
Institut Curie
Université Paris Sud 11
SDSV / FdV
Université Paris Saclay / Université Paris Descartes

Laboratory

Phone: 0169863127
UMR3348
Labex CelTisPhyBio, contrat ANR, équipe FRM

Mots clefs

Neurodegeneration
tubulin code
microtubule cytoskeleton
posttranslational modifications
neuronal differentiation
Available to host a PhD student

publications

Gadadhar S, Dadi H, Bodakuntla S, Schnitzler A, Bieche I, Rusconi F, Janke C (2017) Tubulin glycylation controls primary cilia length. J Cell Biol 216: 2701-2713

Barisic M, Silva e Sousa R, Tripathy SK, Magiera MM, Zaytsev AV, Pereira AL, Janke C, Grishchuk EL, Maiato H (2015) Microtubule detyrosination guides chromosomes during mitosis. Science 348: 799-803

Nirschl JJ, Magiera MM, Lazarus JE, Janke C, Holzbaur ELF (2016) alpha-Tubulin Tyrosination and CLIP-170 Phosphorylation Regulate the Initiation of Dynein-Driven Transport in Neurons. Cell Rep: celrep 2509

Belvindrah R, Natarajan K, Shabajee P, Bruel-Jungerman E, Bernard J, Goutierre M, Moutkine I, Jaglin XH, Savariradjane M, Irinopoulou T, Poncer J-C, Janke C, Francis F (2017) Mutation of the alpha-tubulin Tuba1a leads to straighter microtubules and perturbs neuronal migration. J Cell Biol 216: 2443-2461

Bosch Grau M, Masson C, Gadadhar S, Rocha C, Tort O, Marques Sousa P, Vacher S, Bieche I, Janke C (2017) Alterations in the balance of tubulin glycylation and glutamylation in photoreceptors leads to retinal degeneration. J Cell Sci 130: 938-949

 

Fields of research

Neurogenetics / neurodevelopment

Research Theme

In our ongoing projects, we are using biochemistry, biophysics and structural biology in conjunction with cell and mouse biology to identify the molecular mechanisms by which tubulin posttranslational modifications regulative microtubule behaviour and functions, and which are the cellular and developmental roles of these modifications and the corresponding enzymes. Our functional studies are focussed on the nervous system, cilia and flagella (including spermatogenesis), and cell division. Our team is closely collaborating with clinicians to delineate the implications of tubulin posttranlsational modifications in human pathologies.  

Microtubules are key cytoskeletal elements involved in a large number of functions in eukaryotic cells. They assemble from a protein dimer of a- and b-tubulin, two highly similar and conserved proteins. Tubulins are subject to a large variety of posttranslational modifications, which provide a rapid and reversible mechanism to diversify microtubule functions in cells. Our team is studying the mechanisms and functional roles of these modifications by using an interdisciplinary approach.

Our team has identified the enzymes involved in the posttranslational polyglutamylation (Janke et al, 2005; van Dijk et al, 2007), deglutamylation (Rogowski et al, 2010; Tort et al, 2014) and polyglycylation (Rogowski et al, 2009) of tubulin. Following the discovery of these enzymes, we are now investigating (i) the molecular mechanisms, and (ii) the biological functions of tubulin-modifying enzymes.

Polyglutamylation and polyglycylation take place within the C-terminal tails of the tubulin molecules. These tails are localized at the outer surface of the microtubule, thus their posttranslational modification is most likely regulating the interactions of microtubules with their multiple binding partners, commonly known as microtubule-associated proteins (MAPs) and molecular motors. So far we have demonstrated that the microtubule-severing protein spastin is regulated by tubulin polyglutamylation (Lacroix et al, 2010), and that tubulin glycylation stabilizes ciliary axonemes by a yet unknown molecular mechanism (Bosch Grau et al, 2013; Rogowski et al, 2009). Our functional studies have demonstrated an important role for both, polyglutamylation and polyglycylation for motile and primary cilia in mammals (Bosch Grau et al, 2013; Rocha et al, 2014), and we have found that polyglutamylation is directly linked to neurodegeneration in mice (Rogowski et al, 2010). We have further demonstrated a direct link between altered levels of a tubulin glycylase and colorectal cancer development (Rocha et al, 2014).

Membres de l'équipe

Annemarie Wehenkel
Cecilia Serieyssol
Kathiresan Natarajan
Laurence Vaslin
Maria Magiera
Ngoc-Lan Julie Nguyen
Sudarshan Gadadhar
Tiziana Giordano
Lurlene Akendengue

Lab rotation

Posttranslational modifications of microtubules to control axonal transport

Chercheur responsable: 

JANKE Carsten

Dates: 

2 January 2018 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Jan-March 2018

~ April-June 2018

Project

Polyglutamylation is a posttranslational modification of microtubules, expected to regulate the axonal traffic in neurons. The goal of this rotation is to study the impact of polyglutamylation on axonal traffic using primary hippocampal neurons polyglutamylation-altered mouse lines by live cell imaging.

Contact

Institut Curie - Centre Universitaire, Batiment 110, 91405 Orsay Cedex - +33 1 69 86 31 27 - Maria.Magiera@curie.fr

Superviseur: 

MAGIERA Maria