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Curr Biol. 2019 Dec 18. pii: S0960-9822(19)31578-7. doi: 10.1016/j.cub.2019.11.076. [Epub ahead of print]

Mechanotransduction-Dependent Control of Stereocilia Dimensions and Row Identity in Inner Hair Cells.

Author information

1
Oregon Hearing Research Center & Vollum Institute, Oregon Health & Science University, Portland, OR 97239, USA.
2
Otolaryngology-Head & Neck Surgery, Stanford School of Medicine, Palo Alto, CA 94304, USA.
3
OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, OR 97239, USA; Graduate School of Dentistry, Kyung Hee University, Seoul 02447, South Korea.
4
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA.
5
Oregon Hearing Research Center & Vollum Institute, Oregon Health & Science University, Portland, OR 97239, USA; Oregon Hearing Research Center, Mail Code L335A, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Electronic address: gillespp@ohsu.edu.

Abstract

Actin-rich structures, like stereocilia and microvilli, are assembled with precise control of length, diameter, and relative spacing. By quantifying actin-core dimensions of stereocilia from phalloidin-labeled mouse cochleas, we demonstrated that inner hair cell stereocilia developed in specific stages, where a widening phase is sandwiched between two lengthening phases. Moreover, widening of the second-tallest stereocilia rank (row 2) occurred simultaneously with the appearance of mechanotransduction. Correspondingly, Tmc1KO/KO;Tmc2KO/KO or TmieKO/KO hair cells, which lack transduction, have significantly altered stereocilia lengths and diameters, including a narrowed row 2. EPS8 and the short splice isoform of MYO15A, identity markers for mature row 1 (the tallest row), lost their row exclusivity in transduction mutants. GNAI3, another member of the mature row 1 complex, accumulated at mutant row 1 tips at considerably lower levels than in wild-type bundles. Alterations in stereocilia dimensions and in EPS8 distribution seen in transduction mutants were mimicked by block of transduction channels of cochlear explants in culture. In addition, proteins normally concentrated at mature row 2 tips were also distributed differently in transduction mutants; the heterodimeric capping protein subunit CAPZB and its partner TWF2 never concentrated at row 2 tips like they do in wild-type bundles. The altered distribution of marker proteins in transduction mutants was accompanied by increased variability in stereocilia length. Transduction channels thus specify and maintain row identity, control addition of new actin filaments to increase stereocilia diameter, and coordinate stereocilia height within rows.

KEYWORDS:

Airyscan; actin; development; hair bundle; hair cells; mechanotransduction; myosin; stereocilia

PMID:
31902726
DOI:
10.1016/j.cub.2019.11.076

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