title: Desmin Mutation in the C-Terminal Domain Impairs Traction Force Generation in Myoblasts.
abstract: The cytoskeleton plays a key role in the ability of cells to both resist mechanical stress and generate force, but the precise involvement of intermediate filaments in these processes remains unclear. We focus here on desmin, a type III intermediate filament, which is specifically expressed in muscle cells and serves as a skeletal muscle differentiation marker. By using several complementary experimental techniques, we have investigated the impact of overexpressing desmin and expressing a mutant desmin on the passive and active mechanical properties of C2C12 myoblasts. We first show that the overexpression of wild-type-desmin increases the overall rigidity of the cells, whereas the expression of a mutated E413K desmin does not. This mutation in the desmin gene is one of those leading to desminopathies, a subgroup of myopathies associated with progressive muscular weakness that are characterized by the presence of desmin aggregates and a disorganization of sarcomeres. We show that the expression of this mutant desmin in C2C12 myoblasts induces desmin network disorganization, desmin aggregate formation, and a small decrease in the number and total length of stress fibers. We finally demonstrate that expression of the E413K mutant desmin also alters the traction forces generation of single myoblasts lacking organized sarcomeres.
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Université Paris Diderot, Sorbonne Paris Cité, CNRS, UMR 8251, Paris, France; Matière et Systèmes Complexes, Université Paris Diderot, Sorbonne Paris Cité, CNRS, UMR 7057, Paris, France.
authors.forename: Elisabeth E
authors.initials: EE
authors.lastname: Charrier
authors.affiliation: Matière et Systèmes Complexes, Université Paris Diderot, Sorbonne Paris Cité, CNRS, UMR 7057, Paris, France.
authors.forename: Atef
authors.initials: A
authors.lastname: Asnacios
authors.affiliation: LIPhy Université Grenoble 1, CNRS, UMR 5588, Grenoble, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Milloud
authors.affiliation: LIPhy Université Grenoble 1, CNRS, UMR 5588, Grenoble, France.
authors.forename: Richard
authors.initials: R
authors.lastname: De Mets
authors.affiliation: LIPhy Université Grenoble 1, CNRS, UMR 5588, Grenoble, France.
authors.forename: Martial
authors.initials: M
authors.lastname: Balland
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Université Paris Diderot, Sorbonne Paris Cité, CNRS, UMR 8251, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Delort
authors.affiliation: Matière et Systèmes Complexes, Université Paris Diderot, Sorbonne Paris Cité, CNRS, UMR 7057, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cardoso
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Université Paris Diderot, Sorbonne Paris Cité, CNRS, UMR 8251, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Vicart
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, Université Paris Diderot, Sorbonne Paris Cité, CNRS, UMR 8251, Paris, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Batonnet-Pichon
authors.affiliation: Matière et Systèmes Complexes, Université Paris Diderot, Sorbonne Paris Cité, CNRS, UMR 7057, Paris, France. Electronic address: sylvie.henon@univ-paris-diderot.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hénon
mesh_terms: D000818:Animals; D002460:Cell Line; D003893:Desmin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009038:Motion; D020125:Mutation, Missense; D032446:Myoblasts / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D022502:Stress Fibers / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D003893:Desmin