ArticleFrontiers in molecular neuroscience2017
P2X2 Dominant Deafness Mutations Have No Negative Effect on Wild-Type Isoform: Implications for Functional Rescue and in Deafness Mechanism.
Article in Frontiers in molecular neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Perilymphatic ATP plays a critical role in modulating cochlear function to protect from loud sound induced hearing loss.EBioMedicine · 2026Article
- Upregulation of ATP-purinergic P2×2 receptors in the cochlea over-amplifies hearing sensitivity leading to hyperacusis and attenuation by antagonists.bioRxiv : the preprint server for biology · 2026Article
- Single-dose genome editing therapy rescues auditory and vestibular functions in adult mice with DFNA41 deafness.The Journal of clinical investigation · 2025Article
- Subtype-specific structural features of the hearing loss-associated human P2X2 receptor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ATP-gated P2x7 receptors express at type II auditory nerves and required for efferent hearing control and noise protection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Differential Effects of Hearing Loss Mutations in Homomeric P2X2 and Heteromeric P2X2/3 Receptors.Cells · 2025Article
- P2X2 receptor subunit interfaces are missense variant hotspots, where mutations tend to increase apparent ATP affinity.British journal of pharmacology · 2022Article
- Generation and characterization of a P2rx2 V60L mouse model for DFNA41.Human molecular genetics · 2021Article
- Hearing loss mutations alter the functional properties of human P2X2 receptor channels through distinct mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Molecular determinants for agonist recognition and discrimination in P2X2 receptors.The Journal of general physiology · 2019Article
- Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis.Frontiers in molecular neuroscience · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
The P2X2 receptor is an ATP-gated ion channel, assembled by three subunits. Recently, it has been found that heterozygous mutations of P2X2 V60L and G353R can cause autosomal dominant nonsyndromic hearing loss. However, the underlying mechanism remains unclear. The fact that heterozygous mutations cause deafness suggests that the mutations may have dominant-negative effect (DNE) on wild-type (WT) P2X2 isoforms and/or other partners leading to hearing loss. In this study, the effect of these dominant deafness P2X2 mutations on WT P2X2 was investigated. We found that sole transfection of both V60L and G353R deafness mutants could efficiently target to the plasma membrane, like WT P2X2, but exhibit a significantly reduced response to ATP stimulation. Both mutants reduced the channel conductance, but G353R mutation also altered the voltage dependency. Co-expression with WT P2X2 could restore the response to ATP. As the ratio of WT P2X2 vs. mutants increased, the response to ATP was also increased. Computer modeling confirmed that both V60L and G353R dominant-deafness mutant subunits do not have any negative effect on WT P2X2 subunit, when assembled as a heterotrimer. Improper docking or defective gating is the more likely mechanism for impaired channel function by these P2X2 deafness mutations. These results suggest that P2X2 dominant deafness mutations do not have negative effects on WT P2X2 isoforms, and that adding additional WT P2X2 could rescue the lost channel function caused by the deafness mutations. These P2X2 dominant deafness mutations may have negative-effects on other partners leading to hearing loss.
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