Description du projet
Étude des mécanismes des protéines de liaison à l’actine
L’actine est un composant protéique majeur du cytosquelette qui se retrouve sous forme monomérique et polymérique ou filament. Les filaments d’actine jouent un rôle essentiel dans les fonctions cellulaires telles que la motilité, l’endocytose, la division cellulaire et la contraction musculaire. Les protéines de liaison à l’actine (ABP pour Actin binding proteins) déterminent la structure, l’organisation et la dynamique des filaments d’actine. Cependant, les détails de leurs mécanismes de fonctionnement au sein de leur environnement demeurent obscurs. Le projet SegregActin, financé par le CER, entend déterminer la manière dont les cellules induisent la formation de réseaux d’actine de composition ABP favorable à partir d’un inventaire de constituants cytoplasmiques. Il ambitionne également de déterminer la relation entre la composition en ABP des réseaux d’actine et leurs propriétés géométriques, dynamiques et rhéologiques.
Objectif
"The ability of cells to use the actin cytoskeleton for a diversity of cellular processes is due to the fact that actin filaments, although assembled from identical subunits, are organized in a wide variety of structures of appropriate geometrical, dynamical and rheological properties. Key players in this regulation are specific sets of actin binding proteins (ABPs) interacting with each actin networks, to modulate spatially and temporally their properties.
With this project, I want to understand 1/ how cells can generate the formation of actin structures of appropriate ABP composition from a common pool of cytoplasmic components and 2/ the relationship between the ABP composition of an actin network, its geometrical and dynamical properties, and its response to mechanical deformations.
I will hypothesize that the generation of an actin network of appropriate ABP composition can be explained with an original model, taking into account the facts that 1/ actin filaments in cells are not all structurally identical, but adopt specific conformations that are favored and stabilized by certain families of ABPs; and 2/ the interaction of ABPs with actin depends of the geometrical organization of the filaments.
Because this project imposes to study protein-protein interactions in the presence of multiple partners, I propose to develop an unprecedented strategy combining 1/ ""bottom-up"" reconstitutions, where limited sets of ABPs are added one-by-one in the system to understand their combined activities with actin; and 2/ ""top-down"" reconstitutions with protein extracts prepared from a genetically-tractable organism (the yeast S. cerevisiae), where proteins can be removed one-by-one, in order to study actin network properties in near-physiological conditions.
This project will shed a new light on how cells organize their interior, and will represent a unique opportunity to understand how modifications in the expression of ABPs are associated with actin network defects.
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Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
75794 Paris
France