Gamma-actin is required for cytoskeletal maintenance but not development.
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.
Belyantseva
Inna A
IA
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders/National Institutes of Health, Rockville, MD 20850, USA.
Perrin
Benjamin J
BJ
Sonnemann
Kevin J
KJ
Zhu
Mei
M
Stepanyan
Ruben
R
McGee
JoAnn
J
Frolenkov
Gregory I
GI
Walsh
Edward J
EJ
Friderici
Karen H
KH
Friedman
Thomas B
TB
Ervasti
James M
JM
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
D000199:Actins