ArticleThe Journal of biological chemistry2012
HCN1 and HCN2 proteins are expressed in cochlear hair cells: HCN1 can form a ternary complex with protocadherin 15 CD3 and F-actin-binding filamin A or can interact with HCN2.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- The Contribution of HCN Channelopathies in Different Epileptic Syndromes, Mechanisms, Modulators, and Potential Treatment Targets: A Systematic Review.Frontiers in molecular neuroscience · 2022Pooled it
- Noise induced epigenetic effects: A systematic review.Noise & healthPooled it
- A comprehensive review of HCN channel expression and IJournal of neurophysiology · 2025Review
- Article
- Regulation of HCN Channels by Protein Interactions.Frontiers in physiology · 2022Review
- HCN channels in the mammalian cochlea: Expression pattern, subcellular location, and age-dependent changes.Journal of neuroscience research · 2021Article
- Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers.Journal of neurotrauma · 2020Article
- Detection of BDNF-Related Proteins in Human Perilymph in Patients With Hearing Loss.Frontiers in neuroscience · 2019Article
- TRPV6, TRPM6 and TRPM7 Do Not Contribute to Hair-Cell Mechanotransduction.Frontiers in cellular neuroscience · 2018Article
- Deleting the HCN1 Subunit of Hyperpolarization-Activated Ion Channels in Mice Impairs Acoustic Startle Reflexes, Gap Detection, and Spatial Localization.Journal of the Association for Research in Otolaryngology : JARO · 2017Article
- Cyclophosphamide-induced HCN1 channel upregulation in interstitial Cajal-like cells leads to bladder hyperactivity in mice.Experimental & molecular medicine · 2017Article
- HCN Channels Modulators: The Need for Selectivity.Current topics in medicinal chemistry · 2016Review
- Association of SNPs in LCP1 and CTIF with hearing in 11 year old children: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and the G-EAR consortium.BMC medical genomics · 2015Article
- An N-Terminal ER Export Signal Facilitates the Plasma Membrane Targeting of HCN1 Channels in Photoreceptors.Investigative ophthalmology & visual science · 2015Article
- A di-arginine ER retention signal regulates trafficking of HCN1 channels from the early secretory pathway to the plasma membrane.Cellular and molecular life sciences : CMLS · 2015Article
- The how and why of identifying the hair cell mechano-electrical transduction channel.Pflugers Archiv : European journal of physiology · 2015Review
- Adenylate cyclase 1 (ADCY1) mutations cause recessive hearing impairment in humans and defects in hair cell function and hearing in zebrafish.Human molecular genetics · 2014Article
- Calcium regulates molecular interactions of otoferlin with soluble NSF attachment protein receptor (SNARE) proteins required for hair cell exocytosis.The Journal of biological chemistry · 2014Article
- Filamin A promotes dynamin-dependent internalization of hyperpolarization-activated cyclic nucleotide-gated type 1 (HCN1) channels and restricts Ih in hippocampal neurons.The Journal of biological chemistry · 2014Article
- Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
A unique coupling between HCN1 and stereociliary tip-link protein protocadherin 15 has been described for a teleost vestibular hair-cell model and mammalian organ of Corti (OC) (Ramakrishnan, N. A., Drescher, M. J., Barretto, R. L., Beisel, K. W., Hatfield, J. S., and Drescher, D. G. (2009) J. Biol. Chem. 284, 3227-3238). We now show that Ca(2+)-dependent interaction of the organ of Corti HCN1 and protocadherin 15 CD3 is mediated by amino-terminal sequence specific to HCN1 and is not replicated by analogous specific peptides for HCN2 or HCN4 nor by amino-terminal sequence conserved across HCN isoforms utilized in channel formation. Furthermore, the HCN1-specific peptide binds both phosphatidylinositol (3,4,5)-trisphosphate and phosphatidylinositol (4,5)-bisphosphate but not phosphatidylinositol 4-phosphate. Singly isolated cochlear inner and outer hair cells express HCN1 transcript, and HCN1 and HCN2 protein is immunolocalized to hair-cell stereocilia by both z-stack confocal and pre-embedding EM immunogold microscopy, with stereociliary tip-link and subcuticular plate sites. Quantitative PCR indicates HCN1/HCN2/HCN3/HCN4 = 9:9:1:89 in OC of the wild-type mouse, with HCN4 protein primarily attributable to inner sulcus cells. A mutant form of HCN1 mRNA and protein is expressed in the OC of an HCN1 mutant, corresponding to a full-length sequence with the in-frame deletion of pore-S6 domains, predicted by construct. The mutant transcript of HCN1 is ∼9-fold elevated relative to wild-type levels, possibly representing molecular compensation, with unsubstantial changes in HCN2, HCN3, and HCN4. Immunoprecipitation protocols indicate alternate interactions of full-length proteins; HCN1 can interact with protocadherin 15 CD3 and F-actin-binding filamin A forming a complex that does not include HCN2, or HCN1 can interact with HCN2 forming a complex without protocadherin 15 CD3 but including F-actin-binding fascin-2.
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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.