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

doi:10.1016/j.cell.2010.03.049

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 journal › Article › peer-review

142 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 (Triobp^Δex8/Δex8) that are profoundly deaf. Stereocilia of Triobp^Δex8/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 language	English (US)
Pages (from-to)	786-798
Number of pages	13
Journal	Cell
Volume	141
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2010.03.049
State	Published - May 2010

Keywords

Cellbio
Humdisease
Molneuro

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.cell.2010.03.049

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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

@article{27ce64d584cf47e284b367d1d8618e1f,

title = "Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing",

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.",

keywords = "Cellbio, Humdisease, Molneuro",

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

note = "Funding Information: The authors thank M. Ikeya for advice and vectors, M. Streuli for mononclonal antiserum to TRIOBP-1/5, P. Belyantsev for drawings, and N. Gavara, M. Barzik, R. Chadwick, J. Schultz, and D. Drayna for discussions. This work was supported by NIDCD/NIH R01DC008861 and R01DC009434 to G.I.F., R01 DC004314 to J.R.B., the Wellcome Trust grant 071394/Z/03/Z to G.P.R., the HEC and MoST, Islamabad to S.R., intramural programs of NIDDK, NHLBI, and NIDCD Z01 DK060100 to J.E.H., Z01 DK060100 to J.A.H., Z01 HL004232-08 to J.S., Z01 DC 000064 to A.J.G., and Z01 DC000048 to T.B.F. ",

year = "2010",

month = may,

doi = "10.1016/j.cell.2010.03.049",

language = "English (US)",

volume = "141",

pages = "786--798",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

}

Kitajiri, SI, Sakamoto, T, Belyantseva, IA, Goodyear, RJ, Stepanyan, R, Fujiwara, I, Bird, JE, Riazuddin, S, Riazuddin, S, Ahmed, ZM, Hinshaw, JE, Sellers, J, Bartles, JR, Hammer, JA, Richardson, GP, Griffith, AJ, Frolenkov, GI & Friedman, TB 2010, 'Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing', Cell, vol. 141, no. 5, pp. 786-798. https://doi.org/10.1016/j.cell.2010.03.049

TY - JOUR

T1 - Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing

AU - Kitajiri, Shin Ichiro

AU - Sakamoto, Takeshi

AU - Belyantseva, Inna A.

AU - Goodyear, Richard J.

AU - Stepanyan, Ruben

AU - Fujiwara, Ikuko

AU - Bird, Jonathan E.

AU - Riazuddin, Saima

AU - Riazuddin, Sheikh

AU - Ahmed, Zubair M.

AU - Hinshaw, Jenny E.

AU - Sellers, James

AU - Bartles, James R.

AU - Hammer, John A.

AU - Richardson, Guy P.

AU - Griffith, Andrew J.

AU - Frolenkov, Gregory I.

AU - Friedman, Thomas B.

N1 - Funding Information: The authors thank M. Ikeya for advice and vectors, M. Streuli for mononclonal antiserum to TRIOBP-1/5, P. Belyantsev for drawings, and N. Gavara, M. Barzik, R. Chadwick, J. Schultz, and D. Drayna for discussions. This work was supported by NIDCD/NIH R01DC008861 and R01DC009434 to G.I.F., R01 DC004314 to J.R.B., the Wellcome Trust grant 071394/Z/03/Z to G.P.R., the HEC and MoST, Islamabad to S.R., intramural programs of NIDDK, NHLBI, and NIDCD Z01 DK060100 to J.E.H., Z01 DK060100 to J.A.H., Z01 HL004232-08 to J.S., Z01 DC 000064 to A.J.G., and Z01 DC000048 to T.B.F.

PY - 2010/5

Y1 - 2010/5

N2 - 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.

AB - 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.

KW - Cellbio

KW - Humdisease

KW - Molneuro

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UR - http://www.scopus.com/inward/citedby.url?scp=77953269447&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2010.03.049

DO - 10.1016/j.cell.2010.03.049

M3 - Article

C2 - 20510926

AN - SCOPUS:77953269447

SN - 0092-8674

VL - 141

SP - 786

EP - 798

JO - Cell

JF - Cell

IS - 5

ER -

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

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