ArticleJournal of cellular and molecular medicine2013
Impaired surface expression and conductance of the KCNQ4 channel lead to sensorineural hearing loss.
Article in Journal of cellular and molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- HAP1 interaction with KCNQ4 attenuates channel surface expression and function.Molecules and cells · 2026Article
- KCNQ4 c.546C>G variant is associated with early-onset high-frequency hearing loss, tinnitus, and cardiovascular comorbidities in Taiwanese adults.Scientific reports · 2025Article
- mRNA metabolism regulator human antigen R (HuR) regulates age-related hearing loss in aged mice.Nature aging · 2025Article
- Vestibular hair cells are more prone to damage by excessive acceleration insult in the mouse with KCNQ4 dysfunction.Scientific reports · 2024Article
- A Consolidated Understanding of the Contribution of Redox Dysregulation in the Development of Hearing Impairment.Antioxidants (Basel, Switzerland) · 2024Review
- Overlooked KCNQ4 variants augment the risk of hearing loss.Experimental & molecular medicine · 2023Article
- Valproic Acid Inhibits Progressive Hereditary Hearing Loss in a KCNQ4 Variant Model through HDAC1 Suppression.International journal of molecular sciences · 2023Article
- The Pathological Mechanisms of Hearing Loss Caused byBiomedicines · 2022Review
- Cytosolic Hsp90 Isoform-Specific Functions and Clinical Significance.Biomolecules · 2022Review
- Article
- Cell death-inducing cytotoxicity in truncated KCNQ4 variants associated with DFNA2 hearing loss.Disease models & mechanisms · 2021Article
- A novelMolecular medicine reports · 2021Article
- Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway.Pflugers Archiv : European journal of physiology · 2021Review
- Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss.International journal of molecular sciences · 2021Review
- Molecular simulation of the Kv7.4[ΔS269] mutant channel reveals that ion conduction in the cavity is perturbed due to hydrophobic gating.Biochemistry and biophysics reports · 2021Article
- Kv7 Channels and Excitability Disorders.Handbook of experimental pharmacology · 2021Article
- Auditory Threshold Variability in the SAMP8 Mouse Model of Age-Related Hearing Loss: Functional Loss and Phenotypic Change Precede Outer Hair Cell Loss.Frontiers in aging neuroscience · 2021Article
- Type 1 Diabetes Induces Hearing Loss: Functional and Histological Findings in An Akita Mouse Model.Biomedicines · 2020Article
- Guanylyl Cyclase A/cGMP Signaling Slows Hidden, Age- and Acoustic Trauma-Induced Hearing Loss.Frontiers in aging neuroscience · 2020Article
- A mutually induced conformational fit underlies CaThe Journal of biological chemistry · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
KCNQ4, a voltage-gated potassium channel, plays an important role in maintaining cochlear ion homoeostasis and regulating hair cell membrane potential, both essential for normal auditory function. Mutations in the KCNQ4 gene lead to DFNA2, a subtype of autosomal dominant non-syndromic deafness that is characterized by progressive sensorineural hearing loss across all frequencies. Despite recent advances in the identification of pathogenic KCNQ4 mutations, the molecular aetiology of DFNA2 remains unknown. We report here that decreased cell surface expression and impaired conductance of the KCNQ4 channel are two mechanisms underlying hearing loss in DFNA2. In HEK293T cells, a dramatic decrease in cell surface expression was detected by immunofluorescent microscopy and confirmed by Western blot for the pathogenic KCNQ4 mutants L274H, W276S, L281S, G285C, G285S, G296S and G321S, while their overall cellular levels remained normal. In addition, none of these mutations affected tetrameric assembly of KCNQ4 channels. Consistent with these results, all mutants showed strong dominant-negative effects on the wild-type (WT) channel function. Most importantly, overexpression of HSP90β, a key component of the molecular chaperone network that controls the KCNQ4 biogenesis, significantly increased cell surface expression of the KCNQ4 mutants L281S, G296S and G321S. KCNQ4 surface expression was restored or considerably improved in HEK293T cells mimicking the heterozygous condition of these mutations in DFNA2 patients. Finally, our electrophysiological studies demonstrated that these mutations directly compromise the conductance of the KCNQ4 channel, since no significant change in KCNQ4 current was observed after KCNQ4 surface expression was restored or improved.
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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.