| Autor: |
Webb, S., Underhill, A., Grandi, F. C., Plion, B., Carlton, A. J., Jeng, J-Y., Amariutei, A. E., De Faveri, F., Ceriani, F., Johnson, S. L., Safieddine, S., Kros, C. J., Marcotti, W. |
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| Zdroj: |
Journal of Hearing Science; Sep2024, Vol. 14 Issue 3, p117-118, 2p |
| Abstrakt: |
Introduction: The transduction of acoustic information into electrical signals depends on the mechanically induced displacement of stereociliary bundles projecting from the apical surface of the sensory hair cells. Hair bundle deflection opens mechanoelectrical transducer (MET) channels located at the tips of the shorter rows of adjacent stereocilia. The gating of the MET channels requires force supplied by the tensioning of tip links during sound-induced bundle displacement. The motor protein MYO7A, which is an unconventional myosin responsible for syndromic (Usher 1B) or non-syndromic recessive deafness in humans when mutated, has long been associated with tip-link tensioning, but conclusive evidence is still lacking. In this study, we investigated the role of MYO7A in mature hair cells using conditional knockout mice. Material and methods: The role of MYO7A in mature hair cells was investigated using conditional Myo7afl/flMyo15-cre mice in which the delayed downregulation of the protein allowed normal cochlear development and hearing function up to about postnatal day 20. Patch clamp electrophysiolo-gy was used to record the MET current, which was elicited by displacing the hair bundles of the IHCs and OHCs with a piezo-driven fluid jet. The morphology of the stereociliary bundles and their molecular composition was investigated using immunofluorescence microscopy and scanning electron microscopy. Hearing function was measured using auditory brainstem responses. Results: We found that mature hair cells from MYO7A-deficient mice progressively lose their MET current while still having normal hair bundle morphology (up to at least 1 month of age), albeit with a considerably reduced stiffness. Surprisingly, the resting open probability of the MET channel and its sensitivity to intracellular and extracellular Ca2+ were not affected in the absence of MYO7A. By 2 months of age, the hair bundles of the hair cells started to become disorganised and by 7 months the organ of Corti was almost completely devoid of hair cells. We also found that the progression of hearing loss and deterioration of the stereo-ciliary hair bundles in Myo7a-deficient mice was accelerated by noise insults. Finally, transcriptomic analysis showed that the absence of MYO7A in 1 month-old mice caused the downregulation of a number of genes known to be essential for mechanoelectrical transduction. Conclusions: We found that MYO7A is required for maintaining the functional integrity of the stereociliary hair bundles, but it is not essential for setting the resting tension on the mechanoelectrical transduction complex in mature cochlear hair cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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