MYO7a is required for the functional integrity of the mechanoelectrical transduction complex in the outer hair cells of the adult cochlea.

Myosin-VIIA (MYO7A) in an unconventional myosin responsible for syndromic (Usher 1B) or non-syndromic recessive deafness in humans when mutated. In the cochlea, MYO7A is expressed in the stereocilia of both inner and outer hair cells, where it is believed to act as the motor protein tensioning the mechanoelectrical transducer (MET) channel. Whether this tensioning role is a common feature among both types of cochlear hair cells is unknown. Here we show that MYO7A has a distinct role in adult outer hair cells (OHCs), being crucial for the structural integrity of the MET complex. Postnatal deletion of MYO7A did not affect the staircase structure of the hair bundles but caused a progressive reduction of the size of the MET current without affecting the resting open probability and calcium sensitivity of the MET channel. The hair bundle of OHCs deficient in MYO7A also showed reduced bundle stiffness and was highly susceptible to noise exposure. RNA-sequencing identified the down-regulation of several stereociliary proteins in the Myo7a-deficient cochlea. This study reveals that IHCs and OHCs use different mechanisms to maintain the MET channel in its most sensitive resting open position, and confirms that in OHCs, this mechanism is MYO7A independent.