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

Marcotti, Walter, Corns, Laura F, Goodyear, Richard J, Rzadzinska, Agnieszka K, Avraham, Karen B, Steel, Karen P, Richardson, Guy P and Kros, Corné J (2016) The acquisition of mechano-electrical transducer current adaptation in auditory hair cells requires myosin VI. Journal of Physiology, 594 (13). pp. 3667-3681. ISSN 0022-3751

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Neuroscience
Subjects: Q Science > QP Physiology > QP0351 Neurophysiology and neuropsychology > QP0431 Senses > QP0448 Special senses
Depositing User: Corne Kros
Date Deposited: 06 Jun 2016 10:18
Last Modified: 03 Jul 2019 02:19

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Project NameSussex Project NumberFunderFunder Ref
Mechanisms of aminoglyscoside ototoxicity and drug damage repair in sensory hair cells: towards the design of otoprotective strategies.G1025MRC-MEDICAL RESEARCH COUNCILMR/K005561/1
UnsetUnsetWellcome Trust087377