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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Microtubule dynamics in neuronal differentiation

Objectifs

The objective of the project is to understand the role of detyrosination/re-tyrosination, a specific tubulin post-translational modification, on microtubule dynamics of differentiating neurons.

Résumé

Microtubules, which are composed of alpha/beta-tubulin heterodimers, form a dynamic network involved in several cellular processes including neuronal differentiation. Microtubule dynamics is regulated by proteinic partners which association to microtubule are modulated by post-translational modifications of tubulin, including the detyrosination / re-tyrosination cycle. In this cycle, the C-terminal tyrosine of alpha-tubulin is removed by carboxypeptidases (TCPs) and re-added by a ligase (TTL). Our group demonstrated that tyrosinated-tubulin is vital by analyzing the TTL KO mice. We also recently identified TCP enzymes that remained elusive for 40 years.
In this project, the student will prepare neurons from wild type and transgenic mice (TTL and recently produced TCPs mice) to study the effect on neuronal differentiation by shifting the tyrosination status of tubulin into each extreme. He/her will analyze microtubule dynamics in dendrites, axons and axonal growth cones of the developing neurons in culture, at different stages of maturation.
In a next step, depending on the results obtained, he/her will perform rescue experiments by the expression of wild type or mutated versions of TTL or TCPs in the developing KO neurons.

Méthodes

Techniques used will include cellular biology (primary neuronal cultures), neuron transfection, virus infection, biochemistry, live-imaging microscopy, immunofluorescence.

Références

  • Peris L, Bisbal M, Martinez-Hernandez J, Saoudi Y, Jonckheere J, Rolland M, Sebastien M, Brocard J, Denarier E, Bosc C, Guerin C, Gory-Fauré S, Deloulme JC, Lanté F, Arnal I, Buisson A, Goldberg Y, Blanchoin L, Delphin C, Andrieux A. Nat Commun. 2018 Sep 17;9(1):3775. doi: 10.1038/s41467-018-05869-z. PMID: 30224655 A key function for microtubule-associated-protein 6 in activity-dependent stabilisation of actin filaments in dendritic spines.
  • Aillaud C, Bosc C, Peris L, Bosson A, Heemeryck P, Van Dijk J, Le Friec J, Boulan B, Vossier F, Sanman LE, Syed S, Amara N, Couté Y, Lafanechère L, Denarier E, Delphin C, Pelletier L, Humbert S, Bogyo M, Andrieux A, Rogowski K, Moutin MJ. Science. 2017 Nov 16. pii: eaao4165. doi: 10.1126/science.aao4165. Vasohibins/SVBP are tubulin carboxypeptidases (TCP) that regulate neuron differentiation.
  • Wang N, Bosc c, Ryul Choi S, Boulan B, Peris L, Olieric N, Bao N, Krichen F, Chen L, Andrieux A, Olieric V, Moutin MJ, Steinmetz M, Huang H. Nature Structural & Molecular Biology 2019 (In press) Structural basis of tubulin detyrosination by vasohibin-SVBP enzyme complex and functional implications.

Domaines d'expertise requis

Cell biology, neurobiology, imaging techniques, microscopy

Contacts

Leticia Peris. INSERM researcher
Email : leticia.peris@univ-grenoble-alpes.fr
Tél: 0456520535

Mise à jour le 6 juin 2019

Contacts

Pour une candidature spontanée, envoyez un email à gincomm[at]univ-grenoble-alpes.fr ou utilisez le formulaire de contact.

Pour les stages de licence et de 3ème, voir les modalités de demande spécifiques sur les pages correspondantes. 

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