Actin-Bundling Protein TRIOBP Forms Resilient Rootlets of Hair Cell Stereocilia Essential for Hearing

被引：152

作者：

Kitajiri, Shin-ichiro ^{[1
]}

Sakamoto, Takeshi ^{[3
]}

Belyantseva, Inna A. ^{[1
]}

Goodyear, Richard J. ^{[5
]}

Stepanyan, Ruben ^{[6
]}

Fujiwara, Ikuko ^{[4
]}

Bird, Jonathan E. ^{[1
]}

Riazuddin, Saima ^{[1
]}

Riazuddin, Sheikh ^{[7
]}

Ahmed, Zubair M. ^{[1
]}

Hinshaw, Jenny E. ^{[8
]}

Sellers, James ^{[3
]}

Bartles, James R. ^{[9
]}

Hammer, John A., III ^{[4
]}

Richardson, Guy P. ^{[5
]}

Griffith, Andrew J. ^{[2
]}

Frolenkov, Gregory I. ^{[6
]}

Friedman, Thomas B. ^{[1
]}

机构：

[1] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA

[2] Natl Inst Deafness & Other Commun Disorders, Mol Biol & Genet Sect, NIH, Rockville, MD 20850 USA

[3] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA

[4] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA

[5] Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England

[6] Univ Kentucky, Dept Physiol, Lexington, KY 40536 USA

[7] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 54700, Pakistan

[8] NIDDKD, Struct Cell Biol Sect, NIH, Bethesda, MD 20892 USA

[9] Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA

来源：

CELL | 2010年 / 141卷 / 05期

基金：

英国惠康基金;

关键词：

F-ACTIN; BINDING-PROTEIN; CUTICULAR PLATE; BIRD COCHLEA; MYOSIN-XVA; FILAMENTS; INNER; ELONGATION; MOUSE; ESPIN;

D O I：

10.1016/j.cell.2010.03.049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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(Delta ex8/Delta ex8)) that are profoundly deaf. Stereocilia of Triobp(Delta ex8/Delta ex8) 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.

引用

页码：786 / 798

页数：13

共 37 条

[31]

SPUDICH JA, 1971, J BIOL CHEM, V246, P4866

[32] Fast Adaptation and Ca2+ Sensitivity of the Mechanotransducer Require Myosin-XVa in Inner But Not Outer Cochlear Hair Cells [J].

Stepanyan, Ruben ;

Frolenkov, Gregory I. .

JOURNAL OF NEUROSCIENCE, 2009, 29 (13) :4023-4034

[33] FORMATION OF 2-DIMENSIONAL COMPLEXES OF F-ACTIN AND CROSS-LINKING PROTEINS ON LIPID MONOLAYERS - DEMONSTRATION OF UNIPOLAR ALPHA-ACTININ-F-ACTIN CROSS-LINKING [J].

TAYLOR, KA ;

TAYLOR, DW .

BIOPHYSICAL JOURNAL, 1994, 67 (05) :1976-1983

[34] ACTIN-FILAMENTS, STEREOCILIA, AND HAIR-CELLS OF THE BIRD COCHLEA .2. PACKING OF ACTIN-FILAMENTS IN THE STEREOCILIA AND IN THE CUTICULAR PLATE AND WHAT HAPPENS TO THE ORGANIZATION WHEN THE STEREOCILIA ARE BENT [J].

TILNEY, LG ;

EGELMAN, EH ;

DEROSIER, DJ ;

SAUNDERS, JC .

JOURNAL OF CELL BIOLOGY, 1983, 96 (03) :822-834

[35] ACTIN-FILAMENTS, STEREOCILIA, AND HAIR-CELLS OF THE BIRD COCHLEA .4. HOW THE ACTIN-FILAMENTS BECOME ORGANIZED IN DEVELOPING STEREOCILIA AND IN THE CUTICULAR PLATE [J].

TILNEY, LG ;

DEROSIER, DJ .

DEVELOPMENTAL BIOLOGY, 1986, 116 (01) :119-129

[36] An atomic model of actin filaments cross-linked by fimbrin and its implications for bundle assembly and function [J].

Volkmann, N ;

DeRosier, D ;

Matsudaira, P ;

Hanein, D .

JOURNAL OF CELL BIOLOGY, 2001, 153 (05) :947-956

[37] The deaf jerker mouse has a mutation in the gene encoding the espin actin-bundling proteins of hair cell stereocilia and lacks espins [J].

Zheng, LL ;

Sekerková, G ;

Vranich, K ;

Tilney, LG ;

Mugnaini, E ;

Bartles, JR .

CELL, 2000, 102 (03) :377-385

← 1 2 3 4 →