Role of tau in cytoskeleton-dependent focal adhesion dynamics

Objectives

The main objective is to explore how the remodeling of microtubule and actin networks induced by the neuronal protein tau affect the turnover of focal adhesion structures.

Abstract

Tau is a neuronal microtubule (MT) stabilizer that also interacts with actin and regulates MT-actin interplay. Tau dysfunctions induce neurodegenerative diseases such as Alzheimer’s disease. A milestone in the elucidation of tau toxicity is the understanding of the molecular mechanism by which abnormal tau proteins alter the cytoskeleton. Another major related question is to identify cellular processes impacted by these altered cytoskeleton networks. It has recently been proposed that components of focal adhesions are modulators of tau toxicity in Alzheimer’s disease. Furthermore, MTs emerged as an additional player, together with actin, of focal adhesions, whose dysregulation has been linked to neurodegenerative diseases. The aim of this internship is to determine how pathological forms of tau affect cytoskeleton organizations which in turns impact focal adhesions, a mechanism that might trigger synapse alteration in neurons.

Methods

Immunocytochemistry (confocal imaging), cell culture and patterning, in vitro reconstitution of cytoskeleton network, image analysis (ImageJ).

References

• Elie E et al. (2015) Tau co-organizes dynamic microtubule and actin networks. Sci Rep 5:9964.
• Prezel et al (2018) Tau can switch MT network organizations: from random networks to dynamic and stable bundles. Mol Biol Cell 29, 154-165.
• Fourest-Lieuvin et al. (2023) Controlled Tau Cleavage in Cells Reveals Abnormal Localizations of Tau Fragments. Neuroscience 518:162-177.

Requested domains of expertise

Cell biology, Protein biochemistry, Photonic microscopy, Data analysis, Ability to follow protocols.

Contacts

V. Stoppin-Mellet (MCF)
Email : virginie.stoppin-melletuniv-grenoble-alpes.fr
Phone : +33 (0)4 56 52 06 89