Building and repairing the stereocilia cytoskeleton in mammalian auditory hair cells

Abstract

Despite all recent achievements in identification of the molecules that are essential for the structure and mechanosensory function of stereocilia bundles in the auditory hair cells of mammalian species, we still have only a rudimentary understanding of the mechanisms of stereocilia formation, maintenance, and repair. Important molecular differences distinguishing mammalian auditory hair cells from hair cells of other types and species have been recently revealed. In addition, we are beginning to solve the puzzle of the apparent life-long stability of the stereocilia bundles in these cells. New data link the stability of the cytoskeleton in the mammalian auditory stereocilia with the normal activity of mechanotransduction channels. These data suggest new ideas on how a terminally-differentiated non-regenerating hair cell in the mammalian cochlea may repair and tune its stereocilia bundle throughout the life span of the organism.

Loss of Baiap2l2 destabilizes the transducing stereocilia of cochlear hair cells and leads to deafness

“…Several protein complexes are needed to achieve the extremely precise regulation of the stereocilia actin cytoskeleton required to establish the fine structure of the hair bundle. This includes the regulation of the stereocilia length, which is not only identical within rows and between neighbouring hair cells, but also changes along the cochlea and between rows within each bundle (Tilney et al 1992;Kaltenbach et al 1994;Reviewed by: Barr-Gillespie, 2015;Vélez-Ortega & Frolenkov, 2019).…”

“…The perception of sound depends on the transduction of acoustic information into electrical signals by the sensory hair cells, which requires the opening of mechanically gated ion channels (Fettiplace & Kim, 2014). The hair bundles of cochlear inner and outer hair cells (IHCs and OHCs) consist of three rows of stereocilia, which are cross-linked by several types of extracellular links (Tilney et al 1992;Goodyear et al 2005;Vélez-Ortega & Frolenkov, 2019). In the mammalian cochlea, these mechanoelectrical transducer (MET) channels are located at the tips of the middle and shorter rows of the stereociliary hair bundle that protrude from the apical surface of the hair cells.…”

“…The growth of stereocilia is so tightly regulated that their height within each row is similar not only within a single hair bundle, but also between adjacent bundles, and changes depending on location along the tonotopic axis of the cochlea (Tilney et al 1992;Manor & Kachar, 2008;Petit & Richardson 2009). This indicates a sophisticated level of control over the lengthening and widening of stereocilia, which, in altricial rodents, mainly occurs during late embryonic and early postnatal stages (Roth & Bruns, 1992;Kaltenbach, et al 1994;Zine & Romand, 1996) and involves several actin-binding proteins and unconventional myosin motors (Barr-Gillespie, 2015;Vélez-Ortega & Frolenkov, 2019).…”

“…This indicates a sophisticated level of control over the lengthening and widening of stereocilia, which, in altricial rodents, mainly occurs during late embryonic and early postnatal stages (Roth & Bruns, 1992; Kaltenbach, et al . 1994; Zine & Romand, 1996) and involves several actin‐binding proteins and unconventional myosin motors (Barr‐Gillespie, 2015; Vélez‐Ortega & Frolenkov, 2019).…”

Growth factor and receptor malfunctions associated with human genetic deafness

“…In the inner ear, EPS8 and EPS8L2 are components of an electron‐dense complex of proteins at the tips of hair cell stereocilia, as visualized by transmission electron microscopy. By virtue of their actin remodeling activity, they are important for elongation and maintenance of the precise lengths of stereocilia …”