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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Study of the enzymes of alpha-tubulin detyrosination

Objectifs

The project will aim to characterize the TCP enzymes at the molecular and cellular levels.

Résumé

Microtubules, which are composed of alpha/beta-tubulin heterodimers, form a dynamic network involved in several cellular processes including mitosis, cell motility, intracellular transport and organization of subcellular compartments, cell shape and polarization. The posttranslational modifications of microtubules are centrally involved in their diverse functions. In the detyrosination/tyrosination cycle, the C-terminal tyrosine of alpha-tubulin of is removed by a carboxypeptidase (TCP) and re-added by a ligase (TTL). Tyrosination is critical for mitosis, neuronal physiology, and heart function.
Almost 40 years after the first description of tubulin detyrosination, we recently succeeded to identify the enzymes that are responsible for this process. This finding opens new avenues to unravel the significance of microtubule detyrosination in health and disease, and prompt to the need of characterization of TCP enzymes.
The student will analyze various deletion mutants to clarify the protein domain(s) required for hydrolysis, binding to microtubules and molecular regulation(s). He/she will examine potential phosphorylation regulatory sites in the TCP enzymes by mutagenesis. He/she will also study TCPs functioning on microtubules by video microscopy within cells (fibroblasts, neurons) and on microtubule preparations (TIRF microscopy).

Méthodes

Cells cultures (neurons, fibroblasts, cells from wild type or model animals), transfection, immunofluorescence, production of proteins in E. Coli, Western-blot, videomicroscopy, TIRF.

Références

  • Evidence for new C-terminally truncated variants of alpha- and beta-tubulins. Aillaud et al, Mol Biol Cell. 2016 Feb 15;27(4):640-53.
  • CAP-GLY proteins at microtubule plus ends: is EB1 detyrosination involved? Bosson et al .PLoS One. 2012;7(3):e33490. Epub 2012 Mar 14.
  • A family of protein deglutamylating enzymes associated with neurodegeneration. Rogowski et al. Cell. 2010 Nov 12;143(4):564-78.

Contacts

Marie-Jo Moutin, CR1 CNRS
Email : moutinm@univ-grenoble-alpes.fr

Mise à jour le 7 juillet 2017

Contacts

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Pour les stages de licence et de 3ème, utilisez les formulaires de demande spécifiques : stage de 3ème ou stage de licence UGA. 

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