Dataset Information

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 (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.

SUBMITTER: Kitajiri S

PROVIDER: S-EPMC2879707 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Kitajiri Shin-ichiro S 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

Cell 20100501 5

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 ...[more]

PMID: 20510926

Similar Datasets

Project description:Hearing and vestibular function depend on mechanosensory staircase collections of hair cell stereocilia, which are produced from microvillus-like precursors as their parallel actin bundle scaffolds increase in diameter and elongate or shorten. Hair cell stereocilia contain multiple classes of actin-bundling protein, but little is known about what each class contributes. To investigate the roles of the espin class of actin-bundling protein, we used a genetic approach that benefited from a judicious selection of mouse background strain and an examination of the effects of heterozygosity. A congenic jerker mouse line was prepared by repeated backcrossing into the inbred CBA/CaJ strain, which is known for excellent hearing and minimal age-related hearing loss. We compared stereocilia in wild-type CBA/CaJ mice, jerker homozygotes that lack espin proteins owing to a frameshift mutation in the espin gene, and jerker heterozygotes that contain reduced espin levels. The lack of espins radically impaired stereociliary morphogenesis, resulting in stereocilia that were abnormally thin and short, with reduced differential elongation to form a staircase. Mean stereociliary diameter did not increase beyond ?0.10-0.14 µm, making stereocilia ?30%-60% thinner than wild type and suggesting that they contained ?50%-85% fewer actin filaments. These characteristics indicate a requirement for espins in the appositional growth and differential elongation of the stereociliary parallel actin bundle and fit the known biological activities of espins in vitro and in transfected cells. The stereocilia of jerker heterozygotes showed a transient proximal-distal tapering suggestive of haploinsufficiency and a slowing of morphogenesis that revealed previously unrecognized assembly steps and intermediates. The lack of espins also led to a region-dependent degeneration of stereocilia involving shortening and collapse. We conclude that the espin actin-bundling proteins are required for the assembly and stabilization of the stereociliary parallel actin bundle.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets