Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing

Shin Ichiro Kitajiri, Takeshi Sakamoto, Inna A. Belyantseva, Richard J. Goodyear, Ruben Stepanyan, Ikuko Fujiwara, Jonathan E. Bird, Saima Riazuddin, Sheikh Riazuddin, Zubair M. Ahmed, Jenny E. Hinshaw, James Sellers, James R. Bartles, John A. Hammer, Guy P. Richardson, Andrew J. Griffith, Gregory I. Frolenkov, Thomas B. Friedman*

*Corresponding author for this work

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Inner ear hair cells detect sound through deflection of mechanosensory stereocilia. Each stereocilium is supported by a paracrystalline array of parallel actin filaments that are packed more densely at the base, forming a rootlet extending into the cell body. The function of rootlets and the molecules responsible for their formation are unknown. We found that TRIOBP, a cytoskeleton-associated protein mutated in human hereditary deafness DFNB28, is localized to rootlets. In vitro, purified TRIOBP isoform 4 protein organizes actin filaments into uniquely dense bundles reminiscent of rootlets but distinct from bundles formed by espin, an actin crosslinker in stereocilia. We generated mutant Triobp mice (TriobpΔex8/Δex8) that are profoundly deaf. Stereocilia of TriobpΔex8/Δex8 mice develop normally but fail to form rootlets and are easier to deflect and damage. Thus, F-actin bundling by TRIOBP provides durability and rigidity for normal mechanosensitivity of stereocilia and may contribute to resilient cytoskeletal structures elsewhere.

Original languageEnglish (US)
Pages (from-to)786-798
Number of pages13
JournalCell
Volume141
Issue number5
DOIs
StatePublished - May 2010

Keywords

  • Cellbio
  • Humdisease
  • Molneuro

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kitajiri, S. I., Sakamoto, T., Belyantseva, I. A., Goodyear, R. J., Stepanyan, R., Fujiwara, I., Bird, J. E., Riazuddin, S., Riazuddin, S., Ahmed, Z. M., Hinshaw, J. E., Sellers, J., Bartles, J. R., Hammer, J. A., Richardson, G. P., Griffith, A. J., Frolenkov, G. I., & Friedman, T. B. (2010). Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing. Cell, 141(5), 786-798. https://doi.org/10.1016/j.cell.2010.03.049