Abstract
Sound transduction depends upon mechanosensitive channels localized on the hair-like bundles that project from the apical surface of cochlear hair cells. Hair bundles show a stair-case structure composed of rows of stereocilia, and each stereocilium contains a core of tightly-packed and uniformly-polarized actin filaments. The growth and maintenance of the stereociliary actin core are dynamically regulated. Recently, it was shown that the actin-binding protein gelsolin is expressed in the stereocilia of outer hair cells (OHCs) and in its absence they become long and straggly. Gelsolin is part of a whirlin scaffolding protein complex at the stereocilia tip, which has been shown to interact with other actin regulatory molecules such as Eps8. Here we investigated the physiological effects associated with the absence of gelsolin and its possible overlapping role with Eps8. We found that, in contrast to Eps8, gelsolin does not affect mechanoelectrical transduction during immature stages of development. Moreover, OHCs from gelsolin knockout mice were able to mature into fully functional sensory receptors as judged by the normal resting membrane potential and basolateral membrane currents. Mechanoelectrical transducer current in gelsolin-Eps8 double knockout mice showed a profile similar to that observed in the single mutants for Eps8. We propose that gelsolin has a non-overlapping role with Eps8. While Eps8 is mainly involved in the initial growth of stereocilia in both inner hair cells (IHCs) and OHCs, gelsolin is required for the maintenance of mature hair bundles of low-frequency OHCs after the onset of hearing.
Highlights
The perception of hearing depends on the transduction of sound stimuli into electrical signals that are transmitted to the auditory afferent neurons
Mechanoelectrical transducer (MET) currents were recorded from postnatal day 6 (P6) outer hair cells (OHCs) by displacing their hair bundles in the excitatory and inhibitory direction using a piezo-driven fluidjet (50 Hz sinusoidal force stimulus [17,18])
We have shown that the actin-binding protein gelsolin is not involved in mechano electrical transduction in OHCs from prehearing mice
Summary
The perception of hearing depends on the transduction of sound stimuli into electrical signals that are transmitted to the auditory afferent neurons Crucial to this process is the opening of mechanically gated channels localized near the tips of stereocilia that protrude from the apical surfaces of hair cells to form hair-like bundles [1,2]. The length of each stereocilium is scaled precisely to form the staircase-like structure of each hair bundle, the overall size and shape of which depends on location along the cochlea [6] The development of this precise array of stereocilia mainly occurs during early postnatal stages through a process of elongation and thickening, as well as the elimination of redundant stereocilia [5,6]. Whirlin appears to act as a scaffold to other actin regulatory molecules such as the MAGUK protein p55 [10] and Eps8 [11] and gelsolin has recently been shown to interact with p55 [10]
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