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γ-Actin is required for cytoskeletal maintenance but not development

2009; National Academy of Sciences; Volume: 106; Issue: 24 Linguagem: Inglês

10.1073/pnas.0900221106

1091-6490

Inna A. Belyantseva, Benjamin J. Perrin, Kevin J. Sonnemann, Mei Zhu, Ruben Stepanyan, JoAnn McGee, Gregory I. Frolenkov, Edward J. Walsh, Karen H. Friderici, Thomas B. Friedman, James M. Ervasti,

Ear Surgery and Otitis Media

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.