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Truncation of tau and cytoskeleton alteration in neurons

Objectifs

Truncated forms of tau are present in neurons during brain disorders like Alzheimer’s disease. These truncated proteins may exhibit toxic gain of functions, leading to cytoskeleton changes and neuronal impairments. The main objective is to investigate how tau fragments affect neuronal cytoskeleton properties.

Résumé

Tau is a cytoskeleton-associated protein involved in microtubule and actin regulation, which contributes to the proper functions of neurons. Since the identification of tau as a major component of the neurofibrillary tangles characterizing Alzheimer’s disease, much attention has been given to tau aggregative properties. However, recent studies have proposed that soluble truncated forms of tau exhibit toxic gain of functions, leading to cytoskeleton changes and neuronal impairments. Yet, the mechanisms by which these truncated forms alter microtubule and actin networks are still unknown. The student will explore the cytoskeleton-regulative properties of tau fragments in cultured primary hippocampal neurons transduced with each fragment by the mean of lentiviral vectors, already available in the laboratory. Using live-imaging and super-resolution microscopy, the student will determine the effects of tau fragments on microtubule and actin arrays present in neuronal processes.

Méthodes

Mouse brain dissection, cell culture (primary hippocampal neurons), transduction with lentiviral vectors, live-imaging using spinning confocal microscopy, immunofluorescence, Airyscan confocal microscopy, STED super-resolution microscopy.

Références

Prezel E, Elie A, Delaroche J, Stoppin-Mellet V, Bosc C, Serre L, Fourest-Lieuvin A, Andrieux A, Vantard M, ArnalI (2018) Tau can switch microtubule network organizations: from random networks to dynamic and stable bundles.Mol Biol Cell 29:154-165.

Ramirez-Rios, S., E. Denarier, A. Vinit, E. Prezel, V. Stoppin-Mellet, L. Peris, A. Andrieux, L. Serre, A. Fourest-Lieuvin, and I. Arnal. 2016. Tau antagonizes EB tracking at microtubule ends through a phosphorylation-dependentmechanism. Mol biol cell. 27:2924-34.

Elie, A., E. Prezel, C. Guerin, E. Denarier, S. Ramirez-Rios, L. Serre, A. Andrieux, A. Fourest-Lieuvin, L. Blanchoin, and I. Arnal. 2015. Tau co-organizes dynamic microtubule and actin networks. Scientific reports. 5:9964.

Domaines d'expertise requis

Cellular and molecular biology, optical microscopy, English.

Contacts

Anne Fourest-Lieuvin, PhD
Email : anne.fourest-lieuvin@univ-grenoble-alpes.fr
Phone : 04 56 52 06 89

Téléchargement(s)

GIN_offre-stage-M2_2022-2023_AFourest-Lieuvin_20220707.pdf (PDF, 544639 Ko)

Mise à jour le 8 juillet 2022

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