Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing.
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 (Triobp(Deltaex8/Deltaex8)) that are profoundly deaf. Stereocilia of Triobp(Deltaex8/Deltaex8) 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.
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
Shin-ichiro
S
Kitajiri
Takeshi
T
Sakamoto
Inna A
IA
Belyantseva
Richard J
RJ
Goodyear
Ruben
R
Stepanyan
Ikuko
I
Fujiwara
Jonathan E
JE
Bird
Saima
S
Riazuddin
Sheikh
S
Riazuddin
Zubair M
ZM
Ahmed
Jenny E
JE
Hinshaw
James
J
Sellers
James R
JR
Bartles
John A
JA
Hammer
Guy P
GP
Richardson
Andrew J
AJ
Griffith
Gregory I
GI
Frolenkov
Thomas B
TB
Friedman
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D003638:Deafness / Q000378:metabolism*; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D040542:Mechanotransduction, Cellular; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data
D008840:Microfilament Proteins; C550098:TRIOBP protein, mouse