γ-Actin is required for cytoskeletal maintenance but not development

doi:10.1073/pnas.0900221106

γ-Actin is required for cytoskeletal maintenance but not development

^aLaboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders/National Institutes of Health, Rockville, MD 20850;
^bDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455;
^cMicrobiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824;
^dDepartment of Physiology, University of Kentucky, Lexington, KY 40536;
^fMolecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders/National Institutes of Health, Rockville, MD 20850; and
^eDevelopmental Auditory Physiology Laboratory, Boys Town National Research Hospital, Omaha, NE 68131

Edited by Carl Frieden, Washington University School of Medicine, St. Louis, MO, and approved April 24, 2009
↵¹I.A.B., B.J.P., and K.J.S. contributed equally to this work. (received for review January 8, 2009)

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.

Footnotes

²To whom correspondence should be addressed. E-mail: jervasti{at}umn.edu
Author contributions: I.A.B., B.J.P., K.J.S., R.S., J.M., G.I.F., E.J.W., K.H.F., T.B.F., and J.M.E. designed research; I.A.B., B.J.P., K.J.S., M.Z., R.S., J.M., and G.I.F. performed research; I.A.B., B.J.P., K.J.S., M.Z., R.S., J.M., G.I.F., E.J.W., K.H.F., T.B.F., and J.M.E. analyzed data; and I.A.B., B.J.P., K.J.S., G.I.F., K.H.F., T.B.F., and J.M.E. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0900221106/DCSupplemental.