Abstract
Auditory sensory hair cells depend on stereocilia with precisely regulated lengths to detect sound. Since stereocilia are primarily composed of cross-linked, parallel actin filaments, regulated actin dynamics are essential for controlling stereocilia length. Here, we assessed stereocilia actin turnover by monitoring incorporation of inducibly expressed β-actin-GFP in adult mouse hair cells in vivo and by directly measuring β-actin-GFP turnover in explants. Stereocilia actin incorporation is remarkably slow and restricted to filament barbed ends in a small tip compartment, with minimal accumulation in the rest of the actin core. Shorter rows of stereocilia, which have mechanically-gated ion channels, show more variable actin turnover than the tallest stereocilia, which lack channels. Finally, the proteins ADF and AIP1, which both mediate actin filament severing, contribute to stereocilia length maintenance. Together, the data support a model whereby stereocilia actin cores are largely static, with dynamic regulation at the tips to maintain a critical length.
Highlights
Auditory sensory hair cells depend on stereocilia with precisely regulated lengths to detect sound
We developed a novel system for assessing actin dynamics based on inducible b-actin-green fluorescent protein (GFP) expression
In transgenic mouse lines with constitutive, hair cell-specific Atoh1-Cre expression, b-actin-GFP expression was mosaic in inner hair cells (IHCs), outer hair cells (OHCs) and utricular hair cells (Supplementary Fig. 1a–d)[23]
Summary
Auditory sensory hair cells depend on stereocilia with precisely regulated lengths to detect sound. Auditory and vestibular hair cells are specialized sensory cells in the inner ear that depolarize in response to mechanical force This function depends on a specialized cellular architecture that features a precisely structured bundle of actin-based protrusions on the apical surface of the cell called stereocilia. AIP1 ( called WDR1) synergizes with cofilin to accelerate actin severing and disassembly[10,11,12,13,14] while cooperating with capping protein to regulate filament barbed ends[15,16]. ADF ( called destrin), is a well-known actin-severing protein that is functionally and structurally similar to cofilin[17] These proteins induce breaks in actin filaments and can stimulate actin assembly or disassembly depending on the cellular conditions[18,19,20]. Severing activity is potentially relevant in stereocilia considering that cofilin catalyses the disassembly of F-actin in filopodia[21], which like stereocilia consists of parallel actin filaments crosslinked by fascin protein
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