Etude du rôle de la protéine tau dans la migration cellulaire : interaction entre tau, le cytosquelette et les adhérences focales (description en anglais)

Objectifs

Our objective is to decipher how pathological tau induces focal adhesion defects via the disruption of microtubule and actin networks, mechanisms involved in tumor progression.

Résumé

Tau, a microtubule and actin regulator, plays a key role in neurodegenerative diseases. In many cancers, tau undergoes abnormal modifications, and this dysregulation is often associated with metastasis. Strikingly, recent studies have highlighted a link between the focal adhesion pathway and tau dysfunctions. To explore the hypothesis that altered tau induces focal adhesion defects via the disruption of microtubule and actin networks, cells expressing normal or pathological tau proteins will be seeded on micro-patterns which enables to standardize the organization of the cytoskeleton and focal adhesions. We will thus determine how microtubule and actin modifications induced by tau proteins alter the turnover of focal adhesions. Results will be correlated with the effects of tau proteins on cell migration, investigated by live-imaging experiments.

Méthodes

Cell culture and patterning, transduction with lentiviral vectors, live-imaging using spinning confocal microscopy, immunofluorescence, Airyscan confocal microscopy, quantitative image analysis (ImageJ software)

Référence

- Fourest-Lieuvin et al. (2023) Controlled Tau Cleavage in Cells Reveals Abnormal Localizations of Tau Fragments. Neuroscience 518:162-177.
- Prezel et al. (2018) Tau can switch microtubule network organizations: from random networks to dynamic and stable bundles. Mol Biol Cell 29:154-165.
- Ramirez-Rios,et al. (2016). Tau antagonizes EB tracking at microtubule ends through a phosphorylation-dependent mechanism. Mol Biol Cell. 27:2924-34.

Domaines d'expertise requis

Cellular and molecular biology, optical microscopy, English, statistics.

Contact

Anne Fourest-Lieuvin, PhD, DR
Email : %20anne.fourest-lieuvinuniv-grenoble-alpes.fr (anne[dot]fourest-lieuvin[at]univ-grenoble-alpes[dot]fr)
Téléphone : +33 (0)4 56 52 06 89