title: Vimentin filament organization and stress sensing depend on its single cysteine residue and zinc binding.
abstract: The vimentin filament network plays a key role in cell architecture and signalling, as well as in epithelial-mesenchymal transition. Vimentin C328 is targeted by various oxidative modifications, but its role in vimentin organization is not known. Here we show that C328 is essential for vimentin network reorganization in response to oxidants and electrophiles, and is required for optimal vimentin performance in network expansion, lysosomal distribution and aggresome formation. C328 may fulfil these roles through interaction with zinc. In vitro, micromolar zinc protects vimentin from iodoacetamide modification and elicits vimentin polymerization into optically detectable structures; in cells, zinc closely associates with vimentin and its depletion causes reversible filament disassembly. Finally, zinc transport-deficient human fibroblasts show increased vimentin solubility and susceptibility to disruption, which are restored by zinc supplementation. These results unveil a critical role of C328 in vimentin organization and open new perspectives for the regulation of intermediate filaments by zinc.
authors.affiliation: Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (C.S.I.C.), Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Pérez-Sala
authors.affiliation: Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (C.S.I.C.), Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: Clara L
authors.initials: CL
authors.lastname: Oeste
authors.affiliation: Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (C.S.I.C.), Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: Alma E
authors.initials: AE
authors.lastname: Martínez
authors.affiliation: Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (C.S.I.C.), Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Carrasco
authors.affiliation: Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (C.S.I.C.), Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Garzón
authors.affiliation: Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (C.S.I.C.), Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Cañada
mesh_terms: D000169:Acrodermatitis / Q000378:metabolism* / Q000473:pathology; D003545:Cysteine / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D061848:Optical Imaging; D018384:Oxidative Stress; D058105:Polymerization; D011485:Protein Binding; D040901:Proteomics; D014746:Vimentin / Q000378:metabolism* / Q000648:ultrastructure; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism*
chemical_list: D014746:Vimentin; D015032:Zinc; D003545:Cysteine