ArticleNeuron2018
Mechanotransduction by PCDH15 Relies on a Novel cis-Dimeric Architecture.
Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed.
- Molecular identity of the mechanotransduction machinery in inner ear hair cells and mechanotransduction-linked hearing loss.Fundamental research · 2026Review
- Cryo-EM reveals a right-handed double-helix dimer architecture of PCDH15.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Overlapping expression and co-operative function of the zebrafish pcdh15 paralogs.Communications biology · 2026Article
- The Impact of Pcdh15 Deficiency on Cellular Energy Metabolism and Oxidative Stress, and Its Role and Mechanism in Hearing Loss.Clinical and experimental otorhinolaryngology · 2026Article
- Cadherin-23 mutations cause calcium-dependent, allele-sensitive mechanosensory defects.iScience · 2026Article
- A Novel Intronic Variant Causes Aberrant Splicing of PCDH15 in a Family With Usher Syndrome Type 1F.Molecular genetics & genomic medicine · 2026Article
- The bidirectional interplay between RNA processing and mechanotransduction.Cell reports · 2025Review
- Single-molecule fluorescence microscopy reveals regulatory mechanisms of MYO7A-driven cargo transport in stereocilia of live inner ear hair cells.Nature communications · 2025Article
- Identification of druggable binding sites and small molecules as modulators of TMC1.Communications biology · 2025Article
- Molecular basis of proteolytic cleavage regulation by the extracellular matrix receptor dystroglycan.Structure (London, England : 1993) · 2024Article
- Nanomechanics of wild-type and mutant dimers of the inner-ear tip-link protein protocadherin 15.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Prevention and treatment of peri-implant fibrosis by functionally inhibiting skeletal cells expressing the leptin receptor.Nature biomedical engineering · 2024Article
- Elasticity and Thermal Stability are Key Determinants of Hearing Rescue by Mini-Protocadherin-15 Proteins.bioRxiv : the preprint server for biology · 2024Article
- Emergence of slip-ideal-slip behavior in tip-links serve as force filters of sound in hearing.Nature communications · 2024Article
- Pathophysiology of human hearing loss associated with variants in myosins.Frontiers in physiology · 2024Review
- Nanomechanics of wild-type and mutant dimers of the tip-link protein protocadherin 15.bioRxiv : the preprint server for biology · 2023Article
- Antiparallel dimer structure of CELSR cadherin in solution revealed by high-speed atomic force microscopy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mini-PCDH15 gene therapy rescues hearing in a mouse model of Usher syndrome type 1F.Nature communications · 2023Article
- The tetraspan LHFPL5 is critical to establish maximal force sensitivity of the mechanotransduction channel of cochlear hair cells.Cell reports · 2023Article
- Review
Corrections and comments
- Commented on by
Authors and funding
14 authors.
Funding
Abstract
The tip link, a filament formed by protocadherin 15 (PCDH15) and cadherin 23, conveys mechanical force from sound waves and head movement to open hair-cell mechanotransduction channels. Tip-link cadherins are thought to have acquired structural features critical for their role in mechanotransduction. Here, we biophysically and structurally characterize the unusual cis-homodimeric architecture of PCDH15. We show that PCDH15 molecules form double-helical assemblies through cis-dimerization interfaces in the extracellular cadherin EC2-EC3 domain region and in a unique membrane-proximal domain. Electron microscopy studies visualize the cis-dimeric PCDH15 assembly and reveal the PCDH15 extracellular domain as a parallel double helix with cis cross-bridges at the two locations we defined. The helical configuration suggests the potential for elasticity through helix winding and unwinding. Functional studies in hair cells show that mutations that perturb PCDH15 dimerization contacts affect mechanotransduction. Together, these data reveal the cis-dimeric architecture of PCDH15 and show that dimerization is critical for sensing mechanical stimuli.
Indexed as
Identifiers
What OpenQuestion holds
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.