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Marcotti Kros JPhysiol2016.pdf (1.37 MB)

The acquisition of mechano-electrical transducer current adaptation in auditory hair cells requires myosin VI

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posted on 2023-06-09, 01:29 authored by Walter Marcotti, Laura F Corns, Richard GoodyearRichard Goodyear, Agnieszka K Rzadzinska, Karen B Avraham, Karen P Steel, Guy Richardson, Corne Kros
Mutations in Myo6, the gene encoding the (F-actin) minus end-directed unconventional myosin, myosin VI, cause hereditary deafness in mice (Snell's waltzer) and humans. In the sensory hair cells of the cochlea, myosin VI is expressed in the cell bodies and along the stereocilia that project from the cells’ apical surface. It is required for maintaining the structural integrity of the mechanosensitive hair bundles formed by the stereocilia. In this study we investigate whether myosin VI contributes to mechano-electrical transduction. We report that Ca²+-dependent adaptation of the mechano-electrical transducer (MET) current, which serves to keep the transduction apparatus operating within its most sensitive range, is absent in outer and inner hair cells from homozygous Snell's waltzer mutant mice, which fail to express myosin VI. The operating range of the MET channels is also abnormal in the mutants, resulting in the absence of a resting MET current. We found that cadherin 23, a component of the hair bundle's transient lateral links, fails to be downregulated along the length of the stereocilia in maturing Myo6 mutant mice. MET currents of heterozygous littermates appear normal. We propose that myosin VI, by removing key molecules from developing hair bundles, is required for the development of the MET apparatus and its Ca²+-dependent adaptation.

Funding

Mechanisms of aminoglyscoside ototoxicity and drug damage repair in sensory hair cells: towards the design of otoprotective strategies.; G1025; MRC-MEDICAL RESEARCH COUNCIL; MR/K005561/1

Wellcome Trust; 087377

History

Publication status

  • Published

File Version

  • Published version

Journal

Journal of Physiology

ISSN

0022-3751

Publisher

Wiley-Blackwell

Issue

13

Volume

594

Page range

3667-3681

Department affiliated with

  • Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-06-06

First Open Access (FOA) Date

2016-06-06

First Compliant Deposit (FCD) Date

2016-06-04

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