Marcotti Kros JPhysiol2016.pdf (1.37 MB)
The acquisition of mechano-electrical transducer current adaptation in auditory hair cells requires myosin VI
journal contribution
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 KrosMutations 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 PhysiologyISSN
0022-3751Publisher
Wiley-BlackwellExternal DOI
Issue
13Volume
594Page range
3667-3681Department affiliated with
- Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2016-06-06First Open Access (FOA) Date
2016-06-06First Compliant Deposit (FCD) Date
2016-06-04Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC