Auditory sensory hair cells depend on stereocilia with precisely regulated lengths to detect sound. Since stereocilia are primarily composed of crosslinked, 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. Altogether, the data support a model whereby stereocilia actin cores are largely static, with dynamic regulation at the tips to maintain a critical length.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523390PMC
http://dx.doi.org/10.1038/ncomms7855DOI Listing

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Article Synopsis
  • In the auditory and vestibular systems, stereocilia are specialized structures that convert sound and motion into electrical signals, with their growth involving the addition of actin filaments.
  • Research focused on how stereocilia widen during development, finding that new actin filaments first incorporate at the tips before spreading along the shaft, indicating that the core structure remains stable.
  • The study revealed a previously unrecognized population of short actin filaments at the tips of stereocilia, which are influenced by specific myosin motors (MYO3A/B and MYO15A) that play a crucial role in their growth and stabilization, suggesting these interactions are important for proper mechanosensory function.
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Article Synopsis
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Stub1 promotes degradation of the activated Diaph3: A negative feedback regulatory mechanism of the actin nucleator.

J Biol Chem

October 2024

MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Medical School, Nanjing University, Nanjing, China; Research Institute of Otolaryngology, Nanjing, China. Electronic address:

The formin protein Diaph3 is an actin nucleator that regulates numerous cytoskeleton-dependent cellular processes through the activation of actin polymerization. Expression and activity of Diaph3 is tightly regulated: lack of Diaph3 results in developmental defects and embryonic lethality in mice, while overexpression of Diaph3 causes auditory neuropathy. It is known that Diaph3 homophilic interactions include the intramolecular interaction of its Dia-inhibitory domain (DID)-diaphanous autoregulatory domain (DAD) domains and the intermolecular interactions of DD-DD domains or FH2-FH2 domains.

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The hair bundle, or stereocilia bundle, is the mechanosensory compartment of hair cells (HCs) in the inner ear. To date, most mechanistic studies have focused on stereocilia bundle morphogenesis, and it remains unclear how this organelle critical for hearing preserves its precise dimensions during life in mammals. The GPSM2-GNAI complex occupies the distal tip of stereocilia in the tallest row and is required for their elongation during development.

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Auditory hair cells, which convert sound-induced vibrations in the inner ear into neural signals, depend on multiple actin populations for normal function. Stereocilia are mechanosensory protrusions formed around a core of linear, crosslinked F-actin. They are anchored in the cuticular plate, which predominantly consists of randomly oriented actin filaments.

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