دورية أكاديمية
A Tmc1 mutation reduces calcium permeability and expression of mechanoelectrical transduction channels in cochlear hair cells.
| العنوان: | A Tmc1 mutation reduces calcium permeability and expression of mechanoelectrical transduction channels in cochlear hair cells. |
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| المؤلفون: | Beurg, M, Barlow, A, Furness, DN, Fettiplace, R |
| بيانات النشر: | National Academy of Sciences |
| سنة النشر: | 2019 |
| المجموعة: | Keele University: Keele Research Repository |
| مصطلحات موضوعية: | Q Science (General), QH Natural history |
| الوصف: | Mechanoelectrical transducer (MET) currents were recorded from cochlear hair cells in mice with mutations of transmembrane channel-like protein TMC1 to study the effects on MET channel properties. We characterized a Tmc1 mouse with a single-amino-acid mutation (D569N), homologous to a dominant human deafness mutation. Measurements were made in both Tmc2 wild-type and Tmc2 knockout mice. By 30 d, Tmc1 pD569N heterozygote mice were profoundly deaf, and there was substantial loss of outer hair cells (OHCs). MET current in OHCs of Tmc1 pD569N mutants developed over the first neonatal week to attain a maximum amplitude one-third the size of that in Tmc1 wild-type mice, similar at apex and base, and lacking the tonotopic size gradient seen in wild type. The MET-channel Ca2+ permeability was reduced 3-fold in Tmc1 pD569N homozygotes, intermediate deficits being seen in heterozygotes. Reduced Ca2+ permeability resembled that of the Tmc1 pM412K Beethoven mutant, a previously studied semidominant mouse mutation. The MET channel unitary conductance, assayed by single-channel recordings and by measurements of current noise, was unaffected in mutant apical OHCs. We show that, in contrast to the Tmc1 M412K mutant, there was reduced expression of the TMC1 D569N channel at the transduction site assessed by immunolabeling, despite the persistence of tip links. The reduction in MET channel Ca2+ permeability seen in both mutants may be the proximate cause of hair-cell apoptosis, but changes in bundle shape and protein expression in Tmc1 D569N suggest another role for TMC1 apart from forming the channel. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://eprints.keele.ac.uk/id/eprint/6911/1/D%20Furness%20-%20A%20Tmc1%20mutation%20reduces%20calcium%20permeability%20and%20expression%20of%20mechanoelectrical%20transduction%20channels%20in%20cochlear%20hair%20cells.pdfTest; Beurg, M, Barlow, A, Furness, DN and Fettiplace, R (2019) A Tmc1 mutation reduces calcium permeability and expression of mechanoelectrical transduction channels in cochlear hair cells. Proceedings of the National Academy of Sciences of the United States of America, 116 (41). pp. 20743-20749. |
| DOI: | 10.1073/pnas.1908058116 |
| الإتاحة: | https://doi.org/10.1073/pnas.1908058116Test https://eprints.keele.ac.uk/id/eprint/6911Test/ https://eprints.keele.ac.uk/id/eprint/6911/1/D%20Furness%20-%20A%20Tmc1%20mutation%20reduces%20calcium%20permeability%20and%20expression%20of%20mechanoelectrical%20transduction%20channels%20in%20cochlear%20hair%20cells.pdfTest https://www.pnas.org/content/early/2019/09/18/1908058116Test |
| حقوق: | cc_by_nc_nd_4 |
| رقم الانضمام: | edsbas.A13C232E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1073/pnas.1908058116 |
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