ArticleThe Journal of biological chemistry2012
Excision of Trpv6 gene leads to severe defects in epididymal Ca2+ absorption and male fertility much like single D541A pore mutation.
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 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- TRP Channels Interactome as a Novel Therapeutic Target in Breast Cancer.Frontiers in oncology · 2021Pooled it
- The in vivo TRPV6 protein starts at a non-AUG triplet, decoded as methionine, upstream of canonical initiation at AUG.The Journal of biological chemistry · 2013Trial
- Restoring the FOXO1 geroprotective pathway via seno-resistant mesenchymal progenitor cells alleviates primate epididymal aging.Protein & cell · 2026Article
- Reevaluating the role of TRPV6 deficiency in human and mouse pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- The Impact of Cadmium Telluride Quantum Dots on Male Reproductive Health: A Systematic Review of Toxicological Effects and Mechanisms.The world journal of men's health · 2026Review
- TRPV6 channel function is involved in endometrial epithelial cell CaCellular and molecular life sciences : CMLS · 2025Article
- Targeting TRPV6/CXCR4 complexes prevents castration-resistant prostate cancer metastasis to the bone.Signal transduction and targeted therapy · 2025Article
- Molecular pharmacology of the onco-TRP channel TRPV6.Channels (Austin, Tex.) · 2023Review
- Molecular pathway and structural mechanism of human oncochannel TRPV6 inhibition by the phytocannabinoid tetrahydrocannabivarin.Nature communications · 2023Article
- Exosomes: New regulators of reproductive development.Materials today. Bio · 2023Review
- Characterization of the TRPV6 calcium channel-specific phenotype by RNA-seq in castration-resistant human prostate cancer cells.Frontiers in genetics · 2023Article
- Calcium selective channel TRPV6: Structure, function, and implications in health and disease.Gene · 2022Review
- Calcium Homeostasis in the Epididymal Microenvironment:Frontiers in cell and developmental biology · 2022Review
- Structural mechanisms of TRPV6 inhibition by ruthenium red and econazole.Nature communications · 2021Article
- The transformative impact of extracellular vesicles on developing sperm.Reproduction & fertility · 2021Review
- Structure and function of the calcium-selective TRP channel TRPV6.The Journal of physiology · 2021Review
- Transient Receptor Potential Vanilloid 6 (TRPV6) Proteins Control the Extracellular Matrix Structure of the Placental Labyrinth.International journal of molecular sciences · 2020Article
- Channelopathy of the Pancreas Causes Chronic Pancreatitis.Gastroenterology · 2020Article
- Post-mortem histology in transient receptor potential cation channel subfamily V member 6 (TRPV6) under-mineralising skeletal dysplasia suggests postnatal skeletal recovery: a case report.BMC medical genetics · 2020Article
- Uterine Luminal Epithelium as the Transient Gateway for Embryo Implantation.Trends in endocrinology and metabolism: TEM · 2020Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replacement of aspartate residue 541 by alanine (D541A) in the pore of TRPV6 channels in mice disrupts Ca(2+) absorption by the epididymal epithelium, resulting in abnormally high Ca(2+) concentrations in epididymal luminal fluid and in a dramatic but incomplete loss of sperm motility and fertilization capacity, raising the possibility of residual activity of channels formed by TRPV6(D541A) proteins (Weissgerber, P., Kriebs, U., Tsvilovskyy, V., Olausson, J., Kretz, O., Stoerger, C., Vennekens, R., Wissenbach, U., Middendorff, R., Flockerzi, V., and Freichel, M. (2011) Sci. Signal. 4, ra27). It is known from other cation channels that introducing pore mutations even if they largely affect their conductivity and permeability can evoke considerably different phenotypes compared with the deletion of the corresponding protein. Therefore, we generated TRPV6-deficient mice (Trpv6(-/-)) by deleting exons encoding transmembrane domains with the pore-forming region and the complete cytosolic C terminus harboring binding sites for TRPV6-associated proteins that regulate its activity and plasma membrane anchoring. Using this strategy, we aimed to determine whether the TRPV6(D541A) pore mutant still contributes to residual channel activity and/or channel-independent functions in vivo. Trpv6(-/-) males reveal severe defects in fertility and motility and viability of sperm and a significant increase in epididymal luminal Ca(2+) concentration that is mirrored by a lack of Ca(2+) uptake by the epididymal epithelium. Therewith, Trpv6 excision affects epididymal Ca(2+) handling and male fertility to the same extent as the introduction of the D541A pore mutation, arguing against residual functions of the TRPV6(D541A) pore mutant in epididymal epithelial cells.
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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.