title: Gamma-actin is required for cytoskeletal maintenance but not development.
abstract: Beta(cyto)-actin and gamma(cyto)-actin are ubiquitous proteins thought to be essential building blocks of the cytoskeleton in all non-muscle cells. Despite this widely held supposition, we show that gamma(cyto)-actin null mice (Actg1(-/-)) are viable. However, they suffer increased mortality and show progressive hearing loss during adulthood despite compensatory up-regulation of beta(cyto)-actin. The surprising viability and normal hearing of young Actg1(-/-) mice means that beta(cyto)-actin can likely build all essential non-muscle actin-based cytoskeletal structures including mechanosensory stereocilia of hair cells that are necessary for hearing. Although gamma(cyto)-actin-deficient stereocilia form normally, we found that they cannot maintain the integrity of the stereocilia actin core. In the wild-type, gamma(cyto)-actin localizes along the length of stereocilia but re-distributes to sites of F-actin core disruptions resulting from animal exposure to damaging noise. In Actg1(-/-) stereocilia similar disruptions are observed even without noise exposure. We conclude that gamma(cyto)-actin is required for reinforcement and long-term stability of F-actin-based structures but is not an essential building block of the developing cytoskeleton.
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders/National Institutes of Health, Rockville, MD 20850, USA.
authors.forename: Inna A
authors.initials: IA
authors.lastname: Belyantseva
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Perrin
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Sonnemann
authors.forename: Mei
authors.initials: M
authors.lastname: Zhu
authors.forename: Ruben
authors.initials: R
authors.lastname: Stepanyan
authors.forename: JoAnn
authors.initials: J
authors.lastname: McGee
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Frolenkov
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Walsh
authors.forename: Karen H
authors.initials: KH
authors.lastname: Friderici
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
authors.forename: James M
authors.initials: JM
authors.lastname: Ervasti
mesh_terms: D000199:Actins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003599:Cytoskeleton / Q000502:physiology*; D034381:Hearing Loss / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence
chemical_list: D000199:Actins