ArticleDevelopment (Cambridge, England)2022
C2CD6 regulates targeting and organization of the CatSper calcium channel complex in sperm flagella.
Article in Development (Cambridge, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- A Scalable Flow Cytometry Assay to Evaluate CatSper-mediated CaAndrology · 2026Article
- Molecular Characterization of the Murine Catsper4 Promoter and its Regulation by CREMτ.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- ARMH2 is a cytosolic component of CatSper crucial for sperm function.Nature communications · 2025Article
- Dynamic relocation of PKA regulatory subunits during sperm capacitation: Linking PKA to the CatSper signaling complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Male infertility and perfluoroalkyl and poly-fluoroalkyl substances: evidence for alterations in phosphorylation of proteins and fertility-related functional attributes in bull spermatozoa†.Biology of reproduction · 2024Article
- Scans for Signatures of Selection in Genomes of Wagyu and Buryat Cattle Breeds Reveal Candidate Genes and Genetic Variants for Adaptive Phenotypes and Production Traits.Animals : an open access journal from MDPI · 2024Article
- Review
- CaAnimal cells and systems · 2024Review
- The Cation/Calcium Channel of Sperm (CatSper): A Common Role Played Despite Inter-Species Variation?International journal of molecular sciences · 2023Review
- The Chemosensing Role of CatSper in Mammalian Sperm: An Updated Review.Current issues in molecular biology · 2023Review
- CatSper Calcium Channels: 20 Years On.Physiology (Bethesda, Md.) · 2023Review
- The Role of Sperm Membrane Potential and Ion Channels in Regulating Sperm Function.International journal of molecular sciences · 2023Review
- Morphological and Molecular Bases of Male Infertility: A Closer Look at Sperm Flagellum.Genes · 2023Review
- Mouse sperm energy restriction and recovery (SER) revealed novel metabolic pathways.Frontiers in cell and developmental biology · 2023Article
- The action of physiological and synthetic steroids on the calcium channel CatSper in human sperm.Frontiers in cell and developmental biology · 2023Article
- High-throughput screening method for discovering CatSper inhibitors using membrane depolarization caused by external calcium chelation and fluorescent cell barcoding.Frontiers in cell and developmental biology · 2023Article
- Sperm Energy Restriction and Recovery (SER) Alters Epigenetic Marks during the First Cell Cycle of Development in Mice.International journal of molecular sciences · 2022Article
- 3D structure and in situ arrangements of CatSper channel in the sperm flagellum.Nature communications · 2022Article
- A Review on the Role of Bicarbonate and Proton Transporters during Sperm Capacitation in Mammals.International journal of molecular sciences · 2022Review
- C2cd6-encoded CatSperτ targets sperm calcium channel to CaCell reports · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The CatSper cation channel is essential for sperm capacitation and male fertility. The multi-subunit CatSper complexes form highly organized calcium signaling nanodomains on flagellar membranes. Here, we report identification of an uncharacterized protein, C2CD6, as a subunit of the mouse CatSper complex. C2CD6 contains a calcium-dependent, membrane-targeting C2 domain. C2CD6 associates with the CatSper calcium-selective, core-forming subunits. Deficiency of C2CD6 depletes the CatSper nanodomains from the flagellum and results in male sterility. C2CD6-deficient sperm are defective in hyperactivation and fail to fertilize oocytes both in vitro and in vivo. CatSper currents are present but at a significantly lower level in C2CD6-deficient sperm. Transient treatments with either Ca2+ ionophore, starvation, or a combination of both restore the fertilization capacity of C2CD6-deficient sperm. C2CD6 interacts with EFCAB9, a pH-dependent calcium sensor in the CatSper complex. We postulate that C2CD6 facilitates incorporation of the CatSper complex into the flagellar plasma membrane and may function as a calcium sensor. The identification of C2CD6 may enable the long-sought reconstitution of the CatSper ion channel complex in a heterologous system for male contraceptive development.
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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.