ArticleThe Journal of biological chemistry2011
Cellular and molecular mechanisms of autosomal dominant form of progressive hearing loss, DFNA2.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Molecular mechanisms of function deficiencies in KCNQ1 variants associated with Jervell and Lange-Nielsen syndrome.Channels (Austin, Tex.) · 2025Article
- KCNQ4 c.546C>G variant is associated with early-onset high-frequency hearing loss, tinnitus, and cardiovascular comorbidities in Taiwanese adults.Scientific reports · 2025Article
- Common genetic etiologies of sensorineural hearing loss in Koreans.Genomics & informatics · 2024Review
- A versatile functional interaction between electrically silent KCellular and molecular life sciences : CMLS · 2024Article
- Vestibular hair cells are more prone to damage by excessive acceleration insult in the mouse with KCNQ4 dysfunction.Scientific reports · 2024Article
- Repressor element 1-silencing transcription factor deficiency yields profound hearing loss through KeLife · 2022Article
- The Pathological Mechanisms of Hearing Loss Caused byBiomedicines · 2022Review
- Article
- Cell death-inducing cytotoxicity in truncated KCNQ4 variants associated with DFNA2 hearing loss.Disease models & mechanisms · 2021Article
- AGenes · 2021Article
- Different arrhythmia-associated calmodulin mutations have distinct effects on cardiac SK channel regulation.The Journal of general physiology · 2020Article
- Article
- Cooperativity of KScience advances · 2020Article
- The S2-S3 Loop of Kv7.4 Channels Is Essential for Calmodulin Regulation of Channel Activation.Frontiers in physiology · 2020Article
- Whole-exome sequencing identifies two novel mutations in KCNQ4 in individuals with nonsyndromic hearing loss.Scientific reports · 2018Article
- Genes important for otoneurological diagnostic purposes - current status and future prospects.Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale · 2018Review
- Mechanisms of Calmodulin Regulation of Different Isoforms of Kv7.4 K+ Channels.The Journal of biological chemistry · 2016Article
- Cellular mechanisms of mutations in Kv7.1: auditory functions in Jervell and Lange-Nielsen syndrome vs. Romano-Ward syndrome.Frontiers in cellular neuroscience · 2015Article
- Functional significance of K+ channel β-subunit KCNE3 in auditory neurons.The Journal of biological chemistry · 2014Article
- The role of the cytosolic HSP70 chaperone system in diseases caused by misfolding and aberrant trafficking of ion channels.Disease models & mechanisms · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Despite advances in identifying deafness genes, determination of the underlying cellular and functional mechanisms for auditory diseases remains a challenge. Mutations of the human K(+) channel hKv7.4 lead to post-lingual progressive hearing loss (DFNA2), which affects world-wide population with diverse racial backgrounds. Here, we have generated the spectrum of point mutations in the hKv7.4 that have been identified as diseased mutants. We report that expression of five point mutations in the pore region, namely L274H, W276S, L281S, G285C, and G296S, as well as the C-terminal mutant G321S in the heterologous expression system, yielded non-functional channels because of endoplasmic reticulum retention of the mutant channels. We mimicked the dominant diseased conditions by co-expressing the wild-type and mutant channels. As compared with expression of wild-type channel alone, the blend of wild-type and mutant channel subunits resulted in reduced currents. Moreover, the combinatorial ratios of wild type:mutant and the ensuing current magnitude could not be explained by the predictions of a tetrameric channel and a dominant negative effect of the mutant subunits. The results can be explained by the dependence of cell surface expression of the mutant on the wild-type subunit. Surprisingly, a transmembrane mutation F182L, which has been identified in a pre-lingual progressive hearing loss patient in Taiwan, yielded cell surface expression and functional features that were similar to that of the wild type, suggesting that this mutation may represent redundant polymorphism. Collectively, these findings provide traces of the cellular mechanisms for DFNA2.
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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.