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.
Kitajiri
Shin-ichiro
S
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
Sakamoto
Takeshi
T
Belyantseva
Inna A
IA
Goodyear
Richard J
RJ
Stepanyan
Ruben
R
Fujiwara
Ikuko
I
Bird
Jonathan E
JE
Riazuddin
Saima
S
Riazuddin
Sheikh
S
Ahmed
Zubair M
ZM
Hinshaw
Jenny E
JE
Sellers
James
J
Bartles
James R
JR
Hammer
John A
JA
Richardson
Guy P
GP
Griffith
Andrew J
AJ
Frolenkov
Gregory I
GI
Friedman
Thomas B
TB
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