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Exploring relationships between tubulin (de)tyrosination, microtubule behavior and autophagy

Objectifs

Assessment of autophagy in the brain and heart of mice with impaired microtubule (de)tyrosination.
Evaluation and modulation of autophagy in healthy hippocampal neurons and in the cellular context of Alzheimer's disease.

Résumé

Autophagy is one of the two most important proteolytic systems in the cell and plays a role in many physiological and pathophysiological processes. Microtubules are dynamic cytoskeletal fibers formed from tubulin dimers that have versatile architectures and functions in cells. In particular, they are involved in cellular trafficking and autophagosome formation. The detyrosination/tyrosination cycle, a post-translational modification of tubulin, plays an important role in the transport of cellular organelles and may therefore be involved in autophagy processes. This cycle is controlled by several enzymes among which are the tubulin tyrosine ligase (TTL) and several tubulin carboxypeptidases, the VASH1/2-SVBP complexes and MATCAP which we recently identified (Science 2017, 2022). We are interested in understanding the links between (de)tyrosination mediated by these different enzymes, microtubule behavior and autophagy.

Méthodes

Preparation of protein extracts, immunoblots, cell culture, immunofluorescence, proximity ligation assay, transfection, infection.

Références

Vasohibins/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron differentiation. Aillaud et al. Science. 2017 Dec 15;358(6369):1448-1453. PMID: 29146868

The detyrosination/re-tyrosination cycle of tubulin and its role and dysfunction in neurons and cardiomyocytes
Sanyal et al. Semin Cell Dev Biol 2021 Dec 16;S1084-9521(21)00314-1. PMID: 34924330

Posttranslational modification of microtubules by the MATCAP detyrosinase. Landskron et al. Science. 2022 May 20;376(6595):eabn6020. PMID: 35482892

Tubulin tyrosination regulates synaptic function and is disrupted in Alzheimer's disease. Peris, Parato, Qu et al Brain, awab436, https://doi.org/10.1093/brain/awab436.11 February 2022

Domaines d'expertise requis

Biochemistry, cell biology, microtubule, neuron

Contacts

Marie-Jo Moutin (DR CNRS)
Email : moutinm@univ-grenoble-alpes.fr
Phone : 04 56 52 05 44

Téléchargement(s)

GIN_offre-stage-M2_2022-2023_MJMoutin_20220707.pdf (PDF, 107237 Ko)

Mise à jour le 8 juillet 2022

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