TY - JOUR
T1 - γ-Actin is required for cytoskeletal maintenance but not development
AU - Belyantseva, Inna A.
AU - Perrin, Benjamin J.
AU - Sonnemann, Kevin J.
AU - Zhu, Mei
AU - Stepanyan, Ruben
AU - McGee, Joann
AU - Frolenkov, Gregory I.
AU - Walsh, Edward J.
AU - Friderici, Karen H.
AU - Friedman, Thomas B.
AU - Ervasti, James M.
PY - 2009/6/16
Y1 - 2009/6/16
N2 - βcyto-Actin and γcyto-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 γcyto-actin null mice (Actg1-/-) are viable. However, they suffer increased mortality and show progressive hearing loss during adulthood despite compensatory up-regulation of βcyto- actin. The surprising viability and normal hearing of young Actg1-/- mice means that βcyto-actin can likely build all essential non-muscle actin-based cytoskeletal structures including mechanosensory stereocilia of hair cells that are necessary for hearing. Although γcyto-actin-deficient stereocilia form normally, we found that they cannot maintain the integrity of the stereocilia actin core. In the wild-type, γcyto-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 γcyto-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.
AB - βcyto-Actin and γcyto-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 γcyto-actin null mice (Actg1-/-) are viable. However, they suffer increased mortality and show progressive hearing loss during adulthood despite compensatory up-regulation of βcyto- actin. The surprising viability and normal hearing of young Actg1-/- mice means that βcyto-actin can likely build all essential non-muscle actin-based cytoskeletal structures including mechanosensory stereocilia of hair cells that are necessary for hearing. Although γcyto-actin-deficient stereocilia form normally, we found that they cannot maintain the integrity of the stereocilia actin core. In the wild-type, γcyto-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 γcyto-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.
KW - Actin
KW - Cytoskeleton
KW - Hearing
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U2 - 10.1073/pnas.0900221106
DO - 10.1073/pnas.0900221106
M3 - Article
C2 - 19497859
AN - SCOPUS:67649861392
SN - 0027-8424
VL - 106
SP - 9703
EP - 9708
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 24
ER -