Author/Authors :
Shin-ichiro Kitajiri، نويسنده , , Takeshi Sakamoto، نويسنده , , Inna A. Belyantseva، نويسنده , , Richard J. Goodyear، نويسنده , , Ruben Stepanyan، نويسنده , , Ikuko Fujiwara، نويسنده , , Jonathan E. Bird، نويسنده , , Saima Riazuddin، نويسنده , , Sheikh Riazuddin، نويسنده , , Zubair M. Ahmed، نويسنده , , Pampa Ray and Jenny E. Hinshaw، نويسنده , , James Sellers، نويسنده , , James R. Bartles، نويسنده , , John A. Hammer III، نويسنده , , Guy P. Richardson، نويسنده , , Andrew J. Griffith، نويسنده , , Gregory I. Frolenkov، نويسنده , , Thomas B. Friedman، نويسنده ,
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.
