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Grenoble Institut des Neurosciences

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Understanding the neurocytoskeleton remodeling outside of neurons

Objectifs

The main objectives of this project are 1) to reconstitute in a cell-free environment, the main actin networks found in neurons and 2) to determine if some proteins involved in brain diseases (such as MAP6 and tau) can remodel and impact the actin dynamics.

Résumé

The cell cytoskeleton regulates major biological functions such as cell differentiation, cell migration and immune response to name a few. Interestingly, actin microfilaments and microtubules interact with each other, and this crosstalk is key for many cellular functions in eukaryotic cells like neurons. These highly specialized cells extend long processes (axons and dendrites) that are responsible for nerve cell communication. In many brain diseases, the cytoskeleton is disturbed and proteins such as MAP6 and tau, that can be colocalized with the cytoskeleton, are found either mutated or have an altered expression profile. However, it is not clear to what extent MAP6 and tau are able to directly affect the organization and the dynamic properties of the cytoskeleton. Our objective is to determine the molecular impact of MAP6 and tau on the actin cytoskeleton remodeling in cell-free systems reconstituted from purified proteins. This Learning-By-Building approach will allow us to decipher some of the molecular mechanisms induced by the proteins of interest on the cytoskeleton remodeling.

Méthodes

Protein expression (bacteria) and purification (chromatography, affinity, polymerization strategy), protein labelling, SDS-PAGE. Imaging (video-microscopy, TIRF). Analysis (ImageJ, R).

Références

Prezel E et al. (2018) Tau can switch microtubule network organizations: from random networks to dynamic and stable bundles. Mol Biol Cell 29:154-165.

Peris L et al. (2018) A key function for microtubule-associated-protein 6 in activity-dependent stabilisation of actin filaments in dendritic spines. Nat Comm 9:3775.

Antkowiak et al. (2019) Sizes of actin networks sharing a common environment are determined by the relative rates of assembly PLoS Biol 17(6): e3000317.

Domaines d'expertise requis

Protein biochemistry, photonic microscopy.

Contacts

A. Antkowiak (MCF UGA)
Email : adrien.antkowiak@univ-grenoble-alpes.fr
Phone : +33 (0)4 56 52 05 65

Téléchargement(s)

GIN_offre-stage-M2_2022-2023_AAntkowiak_20220707.pdf (PDF, 102707 Ko)

Mise à jour le 8 juillet 2022

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