Brain actin: understanding a fundamental building block of neuronal function and disease

Objectifs

This project aims to characterize the unique molecular and dynamic properties of brain actin and determine how its assembly is regulated. This fundamental knowledge will provide new insights into cytoskeletal regulation in neuronal function and disease.

Résumé

The actin cytoskeleton is a key regulator of cell architecture, differentiation and function. In neurons, actin dynamics are essential for synaptic organization and plasticity, and their dysregulation is associated with neurological disorders. Despite the existence of multiple actin isoforms, most knowledge of actin dynamics comes from studies of muscle actin. Recent unpublished findings from our lab reveal that brain-purified actin displays distinct assembly properties and cannot coassemble with muscle actin despite sharing more than 90% sequence identity. This suggests that brain actin represents a specialized molecular component with unexplored properties. This project will define the biochemical characteristics of brain actin and determine how its assembly is regulated by actin nucleators, including formins and the Arp2/3 complex. Revealing the molecular properties of brain actin will uncover new principles of cytoskeletal regulation and provide insight into how alterations of cytoskeletal networks involving factors such as Tau contribute to neuronal dysfunction.

Méthodes

Protein expression and purification (chromatography, affinity, polymerization strategy), protein labeling, SDSPAGE and biomimetic assays. Actin dynamics and organization will be monitored by spectrofluorimetry and video/TIRF microscopy. Quantitative analysis will be performed using Fiji/ImageJ, R and/or Python.

Référence

* Elie E et al. (2015) Tau co-organizes dynamic microtubule and actin networks. Sci Rep 5:9964

* 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

* Bagdadi et al. (2024) Stable GDP-tubulin islands rescue dynamic microtubules. J Cell Biol (2024) 223 (8): e202307074

Domaines d'expertise requis

Protein biochemistry, Cytoskeletal regulation, Advanced microscopy, Quantitative imaging, Research collaboration

Contact

Adrien Antkowiak, MCF UGA
Email : adrien.antkowiakuniv-grenoble-alpes.fr
Téléphone : +33 (0)4 56 52 05 65