γ-Actin is required for cytoskeletal maintenance but not development

Abstract

β_cyto-Actin and γ_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 γ_cyto-actin null mice (Actg1^−/−) are viable. However, they suffer increased mortality and show progressive hearing loss during adulthood despite compensatory up-regulation of β_cyto-actin. The surprising viability and normal hearing of young Actg1^−/− mice means that β_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 γ_cyto-actin–deficient stereocilia form normally, we found that they cannot maintain the integrity of the stereocilia actin core. In the wild-type, γ_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 γ_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.