ArticleEMBO reports2019
Proteostasis is essential during cochlear development for neuron survival and hair cell polarity.
Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- The ubiquitin-proteasome system and proteostasis in the cochlea and sensorineural hearing disorders.Molecular biomedicine · 2026Review
- Pharmacological chaperones mitigate noise-induced hearing loss by attenuating sustained PERK activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A deafness-blindness syndrome results from ATF6-based disruption of the unfolded protein response.The Journal of clinical investigation · 2025Article
- Pathophysiological processes underlying hidden hearing loss revealed in Kcnt1/2 double knockout mice.Aging cell · 2024Article
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- Mutations in OSBPL2 cause hearing loss associated with primary cilia defects via sonic hedgehog signaling.JCI insight · 2022Article
- VGLUT3-p.A211V variant fuses stereocilia bundles and elongates synaptic ribbons.The Journal of physiology · 2021Article
- Multiple PDZ domain protein maintains patterning of the apical cytoskeleton in sensory hair cells.Development (Cambridge, England) · 2021Article
- Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate.Nature communications · 2021Article
- Age-Related Changes in the Cochlea and Vestibule: Shared Patterns and Processes.Frontiers in neuroscience · 2021Review
- How Elongator Acetylates tRNA Bases.International journal of molecular sciences · 2020Review
- Homeostatic maintenance and age-related functional decline in the Drosophila ear.Scientific reports · 2020Article
- Elongator Subunit 3 (Elp3) Is Required for Zebrafish Trunk Development.International journal of molecular sciences · 2020Article
- Proteostasis is essential during cochlear development for neuron survival and hair cell polarity.EMBO reports · 2019Article
- Metabolism Meets Translation: Dietary and Metabolic Influences on tRNA Modifications and Codon Biased Translation.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Protein homeostasis is essential to cell function, and a compromised ability to reduce the load of misfolded and aggregated proteins is linked to numerous age-related diseases, including hearing loss. Here, we show that altered proteostasis consequent to Elongator complex deficiency also impacts the proper development of the cochlea and results in deafness. In the absence of the catalytic subunit Elp3, differentiating spiral ganglion neurons display large aggresome-like structures and undergo apoptosis before birth. The cochlear mechanosensory cells are able to survive proteostasis disruption but suffer defects in polarity and stereociliary bundle morphogenesis. We demonstrate that protein aggregates accumulate at the apical surface of hair cells, where they cause a local slowdown of microtubular trafficking, altering the distribution of intrinsic polarity proteins and affecting kinocilium position and length. Alleviation of protein misfolding using the chemical chaperone 4-phenylbutyric acid during embryonic development ameliorates hair cell polarity in Elp3-deficient animals. Our study highlights the importance of developmental proteostasis in the cochlea and unveils an unexpected link between proteome integrity and polarized organization of cellular components.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.