title: Mutations in vimentin disrupt the cytoskeleton in fibroblasts and delay execution of apoptosis.
abstract: To get new insights into the function of the intermediate filament (IF) protein vimentin in cell physiology, we generated two mutant cDNAs, one with a point mutation in the consensus motif in coil1A (R113C) and one with the complete deletion of coil 2B of the rod domain. In keratins and glia filament protein (GFAP), analogous mutations cause keratinopathies and Alexander disease, respectively. Both mutants prevented filament assembly in vitro and inhibited assembly of wild-type vimentin when present in equal amounts. In stably transfected preadipocytes, these mutants caused the complete disruption of the endogenous vimentin network, demonstrating their dominant-negative behaviour. Cytoplasmic vimentin aggregates colocalised with the chaperones alphaB-crystallin and HSP40. Moreover, vimR113C mutant cells were more resistant against staurosporine-induced apoptosis compared to controls. We hypothesise that mutations in the vimentin gene, like in most classes of IF genes, may contribute to distinct human diseases.
authors.affiliation: Institut für Physiologische Chemie, Abteilung für Zellbiochemie and LIMES, Universitätsklinikum Bonn, Nussallee 11, D-53115 Bonn, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Schietke
authors.forename: Dominique
authors.initials: D
authors.lastname: Bröhl
authors.forename: Tatjana
authors.initials: T
authors.lastname: Wedig
authors.forename: Norbert
authors.initials: N
authors.lastname: Mücke
authors.forename: Harald
authors.initials: H
authors.lastname: Herrmann
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Magin
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003593:Cytoplasm; D003599:Cytoskeleton / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D002479:Inclusion Bodies / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D046912:Multiprotein Complexes; D009154:Mutation / Q000235:genetics*; D021381:Protein Transport; D013347:Subcellular Fractions; D014746:Vimentin / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D014783:Viscosity
chemical_list: D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D014746:Vimentin