Affinage

CATSPER1

Cation channel sperm-associated protein 1 · UniProt Q8NEC5

Length
780 aa
Mass
90.1 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CATSPER1 is the principal pore-forming subunit of the CatSper channel, a sperm-specific, multi-subunit Ca²⁺-selective ion channel complex essential for male fertility in both mice and humans. The CatSper channel, composed of CATSPER1–4, CATSPERβ, γ, δ, ε, θ, C2CD6, and EFCAB9, assembles co-dependently such that loss of any single subunit destabilizes the entire complex and abolishes the alkalinization- and voltage-activated Ca²⁺ current (ICatSper) required for hyperactivated motility, egg coat penetration, and fertilization (PMID:14657352, PMID:17227845, PMID:37725640, PMID:38165034). CatSper functions as a polymodal chemosensor directly activated by intracellular pH, membrane depolarization, progesterone, prostaglandins, and diverse small molecules via extracellular binding sites, with upstream regulation by NHE-mediated pH homeostasis and HCO₃⁻/sAC/cAMP/PKA signaling that sensitizes the channel to activation (PMID:21412338, PMID:22354039, PMID:34381781, PMID:30213858, PMID:38366201). Loss-of-function mutations in CATSPER1 cause autosomal-recessive nonsyndromic male infertility in humans, and defective CatSper function represents the most common identified cause of unexplained male infertility (PMID:19344877, PMID:38165034).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2003 High

    Establishing CATSPER1 as the essential pore subunit: prior to this, the cellular function of CATSPER1 was unknown; knockout revealed it is required for depolarization-evoked Ca²⁺ entry and hyperactivated motility, but dispensable for cAMP-driven motility initiation and capacitation signaling.

    Evidence CatSper1 knockout mouse with Ca²⁺ imaging, motility analysis, and immunofluorescence

    PMID:14657352

    Open questions at the time
    • Electrophysiological recording of ICatSper not yet performed
    • Number of pore subunits unknown
    • Mechanism of channel gating undetermined
  2. 2005 High

    Demonstrating obligate co-dependent assembly: CATSPER1 and CATSPER2 require each other for protein stability, establishing that the channel is a heteromeric complex rather than a homomeric channel.

    Evidence Reciprocal KO western blots in CatSper1⁻/⁻ and CatSper2⁻/⁻ mouse sperm

    PMID:16036917

    Open questions at the time
    • Full subunit composition unknown
    • Direct physical interaction not yet shown by co-IP at this stage
  3. 2006 High

    Revealing a physical and functional link between CatSper and voltage-gated CaV3.3 channels: CATSPER1/2 associate with CaV3.3 in human sperm and inhibit T-type current when co-expressed, suggesting cross-regulation between sperm Ca²⁺ conductances.

    Evidence MudPIT proteomics from human sperm, reciprocal Co-IP, electrophysiology in heterologous cells, FRET

    PMID:16740636

    Open questions at the time
    • Physiological significance of CatSper–CaV3.3 interaction in vivo unclear
    • Whether this interaction occurs in mouse sperm unknown
  4. 2007 High

    Defining the tetrameric pore: all four CatSper subunits (1–4) are required for ICatSper, and auxiliary subunit CATSPERβ was identified as a stably associated transmembrane component whose stability depends on CATSPER1.

    Evidence CatSper3/4 KO mice with patch-clamp electrophysiology and Co-IP; affinity purification/MS from transgenic mouse testis for CATSPERβ

    PMID:17227845 PMID:17478420

    Open questions at the time
    • CATSPERγ, δ, ε, θ subunits not yet identified
    • Structure of assembled complex unknown
  5. 2009 High

    Expanding the complex and establishing human disease relevance: CATSPERγ was identified as an additional subunit dependent on CATSPER1, and frameshift mutations in CATSPER1 were shown to cause autosomal-recessive male infertility in humans.

    Evidence Co-IP and KO validation for CATSPERγ; DHPLC/sequencing in consanguineous Iranian families with autozygosity mapping

    PMID:19344877 PMID:19516020

    Open questions at the time
    • Human electrophysiological phenotype of CATSPER1 mutations not yet recorded
    • Full subunit inventory incomplete
  6. 2011 High

    Identifying direct non-genomic progesterone activation and the CATSPERδ subunit: progesterone activates CatSper with near-zero latency incompatible with metabotropic signaling, and CATSPERδ (Tmem146) knockout abolishes ICatSper and fertility, adding another essential subunit.

    Evidence Patch-clamp on human sperm with progesterone; Tmem146 KO mice with electrophysiology and Co-IP

    PMID:21224844 PMID:21412338

    Open questions at the time
    • Identity of the progesterone-binding site on CatSper unknown
    • Structural basis of channel activation undetermined
  7. 2012 High

    Establishing CatSper as a polymodal chemosensor: the channel is directly activated by odorants, cyclic nucleotide analogues, and diverse small molecules via an extracellular binding site, independent of GPCRs and intracellular cAMP.

    Evidence Patch-clamp electrophysiology and Ca²⁺ fluorimetry with pharmacological dissection in human sperm

    PMID:22354039

    Open questions at the time
    • Molecular identity of the extracellular ligand-binding domains unknown
    • Whether polymodal activation is conserved across species unclear
  8. 2013 High

    Delineating CatSper's electrophysiological uniqueness and transcriptional regulation: double KO of Slo3 and CatSper1 eliminated all alkalization-activated currents, proving these are the only two such channels in mouse sperm; environmental pollutant p,p'-DDE was shown to aberrantly activate CatSper; and the CATSPER1 promoter was characterized as bidirectional with CRE, SRY, and SOX9 regulatory elements.

    Evidence Double KO mice with patch-clamp; patch-clamp of p,p'-DDE effects; promoter reporter assays with DNase footprinting

    PMID:23313885 PMID:23980198 PMID:24067601

    Open questions at the time
    • Physiological relevance of endocrine disruptor activation in vivo unknown
    • In vivo transcription factor occupancy at CATSPER1 promoter not confirmed by ChIP
  9. 2015 High

    Identifying female reproductive tract regulation of CatSper: CRISP1 from cumulus cells modulates CatSper channel activity, and a CatSper-deficient human patient demonstrated fertilization failure directly attributable to loss of CatSper function.

    Evidence Patch-clamp with recombinant CRISP1 and CRISP1 KO female mice; electrophysiological phenotyping of infertile patient

    PMID:26416967 PMID:26453676

    Open questions at the time
    • CRISP1 binding site on CatSper unknown
    • Whether CRISP1 regulation is conserved in humans undetermined
  10. 2018 High

    Resolving PKA regulation (species-specific): in mouse sperm, HCO₃⁻/sAC/cAMP/PKA signaling directly up-regulates CatSper current; however, in human sperm, intracellular cAMP/PKA does not activate CatSper — cAMP analogues instead act via an extracellular site, and common PKA inhibitors are off-target CatSper modulators.

    Evidence Patch-clamp with intracellular cAMP injection in mouse sperm; kinetic fluorimetry and patch-clamp in human sperm and CatSper-deficient patient sperm

    PMID:30213858 PMID:32703901

    Open questions at the time
    • PKA phosphorylation sites on CatSper subunits not mapped
    • Structural basis for extracellular cAMP binding unknown
  11. 2021 High

    Defining upstream pH regulation and ligand binding architecture: NHE-mediated pHi homeostasis is required for CatSper activation; all steroids and prostaglandins activate CatSper via two shared binding sites (steroid and prostaglandin) inhibited by Zn²⁺; seminal plasma EVs potentiate CatSper; and progesterone-induced Ca²⁺ oscillations are membrane potential-dependent CatSper events.

    Evidence Patch-clamp with NHE inhibitors; Ca²⁺ fluorimetry with competition assays in CatSper-deficient patient sperm; patch-clamp with EVs; single-cell Ca²⁺ imaging with valinomycin and CatSper inhibitor RU1968

    PMID:33305795 PMID:34381781 PMID:38335261 PMID:38366201

    Open questions at the time
    • Molecular identity of steroid and prostaglandin binding sites not resolved
    • EV component responsible for CatSper potentiation unknown
    • Zn²⁺ binding site not mapped
  12. 2022 High

    Expanding the complex with C2CD6 and demonstrating CatSper's role in swim chirality: C2CD6, a Ca²⁺-dependent C2 domain protein interacting with EFCAB9, is required for CatSper nanodomain assembly and male fertility; CatSper-mediated Ca²⁺ influx controls clockwise sperm path chirality.

    Evidence C2CD6 and EFCAB9 KO mice with patch-clamp, Co-IP, and sperm path analysis; pharmacological CatSper inhibition

    PMID:34919125 PMID:35438819

    Open questions at the time
    • How C2CD6/EFCAB9 regulate channel gating mechanistically unknown
    • Whether chirality function is conserved in human sperm untested
  13. 2023 High

    Identifying CATSPERθ as a trafficking checkpoint: CATSPERθ scaffolds CATSPER4, mediates CatSper dimer formation, and is required for assembled channel trafficking to the flagellum; without it, CatSper is produced in the testis but never reaches the flagellar membrane.

    Evidence Tmem249 KO mice, Co-IP, MS, immunolocalization showing testicular expression but flagellar absence

    PMID:37725640

    Open questions at the time
    • Dimerization interface not structurally resolved
    • Whether CATSPERθ functions similarly in human sperm untested
  14. 2024 High

    Establishing clinical impact at scale: CatSper dysfunction is the most common identified cause of unexplained male infertility; CatSper-deficient sperm cannot undergo hyperactivation or penetrate the zona pellucida, requiring ICSI.

    Evidence Functional CatSper testing in ~2,300 men with patch-clamp validation, zona penetration assays, and IVF/ICSI clinical outcomes

    PMID:38165034

    Open questions at the time
    • Prevalence of specific CATSPER gene variants across populations incomplete
    • Whether partial CatSper deficiency has graded clinical effects unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The high-resolution structure of the assembled multi-subunit CatSper complex, the molecular identity and location of extracellular ligand-binding sites for steroids, prostaglandins, and Zn²⁺, and the precise PKA phosphorylation sites that regulate channel activity remain unresolved.
  • No cryo-EM or X-ray structure of assembled CatSper complex
  • Ligand-binding sites not molecularly mapped
  • Species-specific regulatory differences not fully explained mechanistically

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6
Localization
GO:0005929 cilium 7 GO:0005886 plasma membrane 4
Pathway
R-HSA-382551 Transport of small molecules 5 R-HSA-162582 Signal Transduction 4 R-HSA-1474165 Reproduction 3
Partners
C2CD6CACNA1ICATSPER2CATSPER3CATSPER4CATSPERDCATSPERGEFCAB9
Complex memberships
CatSper channel complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 CatSper1 is essential for depolarization-evoked Ca2+ entry into sperm and for hyperactivated flagellar motility; CatSper1 null sperm lack this voltage-gated Ca2+ entry but retain normal cAMP-mediated activation of motility, CaV channel protein distribution, and capacitation phosphorylation cascades. CatSper1 knockout mouse model, fluorescence Ca2+ imaging, sperm motility analysis, immunofluorescence for ion channel proteins Proceedings of the National Academy of Sciences of the United States of America High 14657352
2005 Stable expression of CatSper1 protein requires CatSper2 and vice versa (co-dependent expression): CatSper1 null sperm lack CatSper2 protein and CatSper2 null sperm lack CatSper1 protein, demonstrating mutual dependence for protein stability. CatSper1 and CatSper2 knockout mouse models, western blotting, RT-PCR, Ca2+ imaging, sperm motility analysis The Journal of biological chemistry High 16036917
2007 All four CatSper proteins (CatSper1-4) are required to form functional ICatSper current; targeted disruption of CatSper3 or CatSper4 abolishes the alkalinization-activated, voltage-sensitive Ca2+-selective current, hyperactivated motility, and male fertility. Direct protein interactions among CatSpers indicate they form a specialized flagellar channel complex. CatSper3 and CatSper4 knockout mice, patch-clamp electrophysiology, sperm motility analysis, co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 17227845
2007 CatSperβ is an auxiliary transmembrane subunit of the CatSper channel complex purified from mouse testis; it is absent in CatSper1-null sperm, indicating its stability/trafficking depends on CatSper1. Transgenic CatSper1 complex purification from mouse testis, mass spectrometry identification, western blot in CatSper1-/- sperm, immunolocalization The Journal of biological chemistry High 17478420
2009 CatSperγ (CATSPERG) is a novel single-transmembrane subunit of the CatSper channel complex; it is absent in CatSper1-deficient sperm, indicating CatSper1 is required for its trafficking/assembly. Co-immunoprecipitation, western blot in CatSper1-/- sperm, immunolocalization to principal piece Biology of reproduction Medium 19516020
2009 CATSPER1 frameshift insertion mutations (c.539-540insT and c.948-949insATGGC) cause autosomal-recessive nonsyndromic male infertility in humans, establishing CATSPER1 as an essential human male fertility gene. DHPLC and bidirectional sequencing of CATSPER1 in consanguineous Iranian families with autozygosity mapping American journal of human genetics High 19344877
2009 The fast phase of BSA-induced Ca2+ rise during sperm capacitation requires the CatSper channel and is independent of G-proteins and phospholipase C; the Ca2+ signal originates in the principal piece and propagates toward the sperm head. Ca2+ imaging with Fluo-4/Fura-2 in wild-type vs. CatSper1 knockout mouse sperm, EGFP-CATSPER1 rescue experiment, pharmacological inhibitors Reproductive biology and endocrinology High 19860887
2011 Progesterone directly activates the CatSper channel in human sperm, producing Ca2+ influx with almost no latency incompatible with metabotropic signaling; this activation is inhibited by CaV channel blockers NNC 55-0396 and mibefradil. Alkaline pH and progesterone both enhance the CatSper current recorded by patch-clamp. Patch-clamp electrophysiology on human sperm, fluorometric Ca2+ imaging, pharmacological inhibitors Nature High 21412338
2011 CATSPERδ (encoded by Tmem146) is an essential transmembrane subunit of the CatSper channel complex; mice lacking CATSPERδ are infertile with sperm lacking both Ca2+ current and hyperactivated motility, indicating CATSPERδ is required for CatSper channel assembly and/or transport. Tmem146 knockout mice, patch-clamp electrophysiology, sperm motility analysis, co-immunoprecipitation, immunolocalization Nature communications High 21224844
2012 CatSper functions as a polymodal chemosensor directly activated by diverse ligands including odorants and membrane-permeable cyclic nucleotide analogues via an extracellular binding site, without involving GPCRs or cAMP signaling pathways. Patch-clamp electrophysiology, Ca2+ fluorimetry, pharmacological dissection in human sperm The EMBO journal High 22354039
2006 CatSper1 and CatSper2 physically associate with the T-type voltage-gated Ca2+ channel CaV3.3 in human sperm; co-expression of CatSper1 or CatSper2 specifically inhibits CaV3.3-evoked T-type Ca2+ current amplitude without altering other biophysical properties, and the proteins co-localize on the sperm principal piece confirmed by FRET. Multidimensional protein identification technology (MudPIT) from human sperm, co-immunoprecipitation in transfected mammalian cells, electrophysiology, immunostaining, FRET The Journal of biological chemistry High 16740636
2014 CatSper mediates the chemoattractant-evoked Ca2+ influx in sea urchin (Arbacia punctulata) sperm flagella; concomitant alkalinization serves as a highly cooperative mechanism enabling CatSper to transduce periodic voltage changes into Ca2+ bursts for chemotactic steering. Pharmacological inhibition, Ca2+ imaging, electrophysiology in sea urchin sperm, comparison with mammalian CatSper The EMBO journal High 25535245
2013 CatSper activation in human sperm (by progesterone or alkaline pH) promotes penetration into viscous media but does not induce hyperactivation; mobilization of stored Ca2+ (not CatSper) is required for sustained hyperactivation, revealing distinct functional roles for the two Ca2+ signaling sources. CatSper inhibitor NNC55-0396, Ca2+ imaging, CASA motility analysis, methylcellulose penetration assay, thimerosal Ca2+ store mobilization The Journal of biological chemistry Medium 23344959
2013 Simultaneous genetic deletion of Slo3 and CatSper1 abolishes all alkalization- and voltage-activated membrane currents in mouse sperm, demonstrating that KSPER and CatSper are the sole ion channels in mouse sperm regulating membrane potential and Ca2+ influx in response to alkalization. Double knockout mice (Slo3-/-/CatSper1-/-), patch-clamp electrophysiology The Journal of general physiology High 23980198
2015 CRISP1, expressed by cumulus cells surrounding the egg, directly regulates CatSper channel activity in sperm as demonstrated by patch-clamp recordings; this modulates sperm hyperactivation and orientation required for cumulus penetration during fertilization. Patch-clamp electrophysiology on sperm, CRISP1 KO female mice, in vitro fertilization assay, Ca2+ imaging The Journal of cell biology High 26416967
2018 CatSper channel activity is up-regulated by PKA-dependent phosphorylation in mouse sperm: HCO3- activates sAC→cAMP→PKA, which increases CatSper-mediated Ca2+ influx and monovalent cation conductance; direct cAMP injection through the patch pipette activates CatSper current, blocked by PKA inhibitors PKI, H89, and Rp-cAMPS. Patch-clamp electrophysiology with intracellular cAMP injection, Ca2+ imaging, pharmacological PKA inhibitors, CatSper-KO sperm controls The Journal of biological chemistry High 30213858
2020 Human CatSper is not activated by intracellular cAMP or by the cAMP/PKA signaling pathway; instead, nonphysiological concentrations of cAMP and membrane-permeable cAMP analogues activate CatSper from outside via an extracellular binding site, and common PKA inhibitors act as off-target drugs on CatSper itself. Kinetic ion-sensitive fluorometry, patch-clamp recordings, optochemistry in human sperm from donors and CatSper-deficient patients The Journal of biological chemistry High 32703901
2022 C2CD6, containing a calcium-dependent C2 membrane-targeting domain, is a subunit of the mouse CatSper complex; C2CD6 deficiency depletes CatSper nanodomains from the flagellum, reduces CatSper currents, causes male sterility and defective hyperactivation. C2CD6 interacts with EFCAB9, a pH-dependent Ca2+ sensor in the CatSper complex. C2CD6 knockout mice, patch-clamp electrophysiology, immunoprecipitation, in vitro and in vivo fertilization assays, Ca2+ ionophore rescue experiments Development (Cambridge, England) High 34919125
2021 Cdc42 co-localizes with CatSper in four linear domains of the principal piece (distribution disrupted in CatSper1-null sperm); Cdc42 inhibition impairs CatSper activity and modulates cAMP production by soluble adenylate cyclase, revealing a regulatory mechanism linking Cdc42 to CatSper-mediated Ca2+ homeostasis. Immunofluorescence localization, CatSper1-null sperm, Cdc42 pharmacological inhibition, patch-clamp electrophysiology, fertilization assays FASEB journal Medium 34224609
2021 Progesterone-induced [Ca2+]i oscillations in human sperm originate in the flagellum and are driven by membrane potential-sensitive Ca2+ influx through CatSper channels, as demonstrated by suppression with valinomycin (membrane hyperpolarization) and the specific CatSper inhibitor RU1968. Fluorescence single-cell Ca2+ imaging, whole-cell current clamp, valinomycin membrane potential manipulation, CatSper inhibitor RU1968 Human reproduction (Oxford, England) High 33305795
2021 NHE-mediated flagellar pHi homeostasis is required for CatSper and KSper channel activation in human sperm; NHE inhibition acidifies flagellar pHi, suppresses alkalization-induced CatSper and KSper currents, and impairs sperm hyperactivation, tyrosine phosphorylation, and progesterone-induced acrosome reaction. Patch-clamp electrophysiology, pHi fluorescent imaging, Ca2+ imaging, computer-assisted sperm motility analysis, immunofluorescence Human reproduction (Oxford, England) High 38366201
2021 Seminal plasma extracellular vesicles (EVs) increase sperm [Ca2+]i via extracellular Ca2+ influx through CatSper channels; EVs potentiate CatSper currents (confirmed by patch-clamp), and EV-induced Ca2+ signals are absent in CatSper-deficient sperm, enhancing hyperactivated motility. Patch-clamp electrophysiology, Ca2+ fluorimetry, CatSper-deficient patient sperm, computer-assisted sperm analysis Human reproduction (Oxford, England) High 38335261
2023 CATSPERθ (encoded by Tmem249) is a transmembrane CatSper subunit that scaffolds the pore-forming subunit CATSPER4 and self-interacts, facilitating CatSper dimer formation; CATSPERθ-null male mice are infertile with sperm lacking the entire CatSper channel from flagella despite normal testicular expression, identifying CATSPERθ as a checkpoint for properly assembled CatSper complex trafficking to flagella. Tmem249 knockout mice, mass spectrometry, co-immunoprecipitation, immunolocalization, sperm motility analysis, fertility assays Proceedings of the National Academy of Sciences of the United States of America High 37725640
2022 CatSper and its Ca2+ sensor EFCAB9 are necessary for clockwise swim path chirality of mouse sperm; sperm lacking the entire CatSper channel or EFCAB9 lose chirality, as does pharmacological CatSper inhibition, demonstrating that CatSper-mediated Ca2+ influx controls directional swimming geometry. CatSper and EFCAB9 knockout mice, pharmacological inhibitors (mibefradil, NNC 55-0396), sperm path analysis FASEB journal High 35438819
2024 CatSper-deficient human sperm are unable to undergo hyperactivated motility and fail to penetrate the egg coat, demonstrating that CatSper-mediated hyperactivation is required for human fertilization; defective CatSper function (caused by CATSPER gene variants) is the most common cause of unexplained male infertility identified, with ICSI required to bypass it. Motility-based CatSper functional test in ~2,300 men, patch-clamp electrophysiology, zona pellucida penetration assay, CATSPER gene sequencing, IVF/ICSI clinical outcomes The Journal of clinical investigation High 38165034
2013 p,p'-DDE activates CatSper in human sperm at environmentally relevant concentrations, increasing CatSper currents by >100% as confirmed by whole-cell patch-clamp, causing extracellular Ca2+ influx and premature acrosome reaction. Whole-cell patch-clamp electrophysiology, Ca2+ single-cell imaging, CatSper inhibitors (mibefradil, NNC 55-0396), acrosome reaction assay Human reproduction (Oxford, England) High 24067601
2021 All steroids and prostaglandins in reproductive fluids activate CatSper via shared binding sites (a steroid-binding site and a prostaglandin-binding site); hormones compete for these sites, and Zn2+ suppresses steroid/prostaglandin action on CatSper, potentially preventing premature CatSper activation in the ejaculate. Ca2+ fluorimetry in human sperm and CATSPER2-deficient patient sperm, structure-activity relationship analysis, pharmacological competition assays Frontiers in cell and developmental biology High 34381781
2015 A man with near-absent CatSper current (confirmed by patch-clamp electrophysiology) failed to respond to progesterone-induced CatSper activation, showed no penetration of viscous media upon CatSper stimulation, and experienced fertilization failure at IVF, providing direct evidence that CatSper dysfunction alone causes human infertility. Whole-cell patch-clamp electrophysiology, Ca2+ imaging, viscous media penetration assay, IVF clinical outcome, CATSPER gene sequencing Human reproduction (Oxford, England) High 26453676
2021 HCO3- in semen activates the soluble adenylyl cyclase/PKA pathway to increase intracellular pH, which sensitizes CatSper to respond to membrane depolarization; this conserved mechanism operates in both human and mouse ejaculated sperm but not in epididymal sperm, explaining species-specific differences in CatSper activation. Ca2+ imaging in ejaculated and epididymal sperm from mouse and human, PKA inhibitors, soluble adenylyl cyclase inhibitors, KCl depolarization, pH manipulation Frontiers in cell and developmental biology Medium 34650979
2017 CCR6 receptor co-localizes and physically interacts with CatSper in human sperm; CCR6 is required for CatSper-mediated Ca2+ entry induced by physiological ligands DEFB1, CCL20, and progesterone. Co-immunoprecipitation, Ca2+ imaging, patch-clamp electrophysiology, CCR6 knockdown, immunolocalization Oncotarget Medium 29207656
2018 A homozygous in-frame 6-bp deletion in exon 18 of CATSPERE (rs761237686) in a patient causes loss of CatSper function and fertilization failure, identifying CATSPERE as a functionally essential subunit of the human CatSper complex. Exome sequencing, Sanger sequencing confirmation, electrophysiology and clinical outcome from previously characterized CatSper-deficient patient Human reproduction (Oxford, England) Medium 30239785
2013 The Catsper1 gene promoter is bidirectional, lacks a TATA box, contains a conserved CRE site, and has multiple transcription initiation sites; SRY, SOX9 and CREB binding sites in the murine promoter are protected by testicular nuclear proteins. Promoter cloning, luciferase reporter assays in HEK293/Sertoli/GC-1spg cells, in vivo testicular injection, RLM-RACE, DNase footprinting Molecular human reproduction Medium 23313885
2018 Human CATSPER1 promoter is positively regulated by CREB1 and CREMτ transcription factors via CRE sites; CRE0 site near the transcription start site is essential for spermatogonial cell activity, while CRE1 site negatively regulates promoter activity. Dual-luciferase reporter assays in HEK293 and GC1-spg cells with CRE site mutations and transcription factor overexpression Archives of medical research Medium 30017233

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm. Nature 433 21412338
2007 All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility. Proceedings of the National Academy of Sciences of the United States of America 410 17227845
2003 CatSper1 required for evoked Ca2+ entry and control of flagellar function in sperm. Proceedings of the National Academy of Sciences of the United States of America 297 14657352
2012 The CatSper channel: a polymodal chemosensor in human sperm. The EMBO journal 184 22354039
2009 Human male infertility caused by mutations in the CATSPER1 channel protein. American journal of human genetics 172 19344877
2011 A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa. Nature communications 166 21224844
2010 The role of Hv1 and CatSper channels in sperm activation. The Journal of physiology 151 20679352
2005 Identical phenotypes of CatSper1 and CatSper2 null sperm. The Journal of biological chemistry 143 16036917
2007 CatSperbeta, a novel transmembrane protein in the CatSper channel complex. The Journal of biological chemistry 133 17478420
2013 Ca2+ signals generated by CatSper and Ca2+ stores regulate different behaviors in human sperm. The Journal of biological chemistry 122 23344959
2010 Genetic male infertility and mutation of CATSPER ion channels. European journal of human genetics : EJHG 114 20648059
2014 The CatSper calcium channel in human sperm: relation with motility and involvement in progesterone-induced acrosome reaction. Human reproduction (Oxford, England) 104 24430778
2009 A novel, single, transmembrane protein CATSPERG is associated with CATSPER1 channel protein. Biology of reproduction 99 19516020
2014 CatSper channel, sperm function and male fertility. Reproductive biomedicine online 96 25457194
2009 The BSA-induced Ca2+ influx during sperm capacitation is CATSPER channel-dependent. Reproductive biology and endocrinology : RB&E 96 19860887
2014 The CatSper channel controls chemosensation in sea urchin sperm. The EMBO journal 79 25535245
2015 Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa. Human reproduction (Oxford, England) 77 26453676
2015 CRISP1 as a novel CatSper regulator that modulates sperm motility and orientation during fertilization. The Journal of cell biology 73 26416967
2007 Expression of CatSper family transcripts in the mouse testis during post-natal development and human ejaculated spermatozoa: relationship to sperm motility. Molecular human reproduction 69 17347248
2013 CatSper and the relationship of hyperactivated motility to intracellular calcium and pH kinetics in equine sperm. Biology of reproduction 65 24048572
2013 p,p'-DDE activates CatSper and compromises human sperm function at environmentally relevant concentrations. Human reproduction (Oxford, England) 62 24067601
2018 CatSper channels are regulated by protein kinase A. The Journal of biological chemistry 60 30213858
2018 A novel cross-species inhibitor to study the function of CatSper Ca2+ channels in sperm. British journal of pharmacology 58 29723408
2017 Exposure to Cadmium Impairs Sperm Functions by Reducing CatSper in Mice. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 55 28554186
2013 Simultaneous knockout of Slo3 and CatSper1 abolishes all alkalization- and voltage-activated current in mouse spermatozoa. The Journal of general physiology 48 23980198
2018 Homozygous in-frame deletion in CATSPERE in a man producing spermatozoa with loss of CatSper function and compromised fertilizing capacity. Human reproduction (Oxford, England) 46 30239785
2015 Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque. Biology of reproduction 42 26490839
2009 Up-regulation of CatSper genes family by selenium. Reproductive biology and endocrinology : RB&E 41 19917098
2005 Positive selection for indel substitutions in the rodent sperm protein catsper1. Molecular biology and evolution 41 15930155
2020 The Ca2+ channel CatSper is not activated by cAMP/PKA signaling but directly affected by chemicals used to probe the action of cAMP and PKA. The Journal of biological chemistry 40 32703901
2019 Release of Porcine Sperm from Oviduct Cells is Stimulated by Progesterone and Requires CatSper. Scientific reports 40 31862909
2016 Bisphenol A Impairs Mature Sperm Functions by a CatSper-Relevant Mechanism. Toxicological sciences : an official journal of the Society of Toxicology 40 27125968
2013 Levels of Tektin 2 and CatSper 2 in normozoospermic and oligoasthenozoospermic men and its association with motility, fertilization rate, embryo quality and pregnancy rate. Journal of assisted reproduction and genetics 40 23519396
2016 Diethylstilbestrol activates CatSper and disturbs progesterone actions in human spermatozoa. Human reproduction (Oxford, England) 39 28031325
2021 Roles of CatSper channels in the pathogenesis of asthenozoospermia and the therapeutic effects of acupuncture-like treatment on asthenozoospermia. Theranostics 38 33456575
2015 Quantification of CatSper1 expression in human spermatozoa and relation to functional parameters. Human reproduction (Oxford, England) 31 25983333
2024 Human fertilization in vivo and in vitro requires the CatSper channel to initiate sperm hyperactivation. The Journal of clinical investigation 29 38165034
2019 Comparative genomic analysis suggests that the sperm-specific sodium/proton exchanger and soluble adenylyl cyclase are key regulators of CatSper among the Metazoa. Zoological letters 26 31372239
2017 Complex CatSper-dependent and independent [Ca2+]i signalling in human spermatozoa induced by follicular fluid. Human reproduction (Oxford, England) 26 28938737
2017 Genomic identification, expression profiling, and functional characterization of CatSper channels in the bovine. Biology of reproduction 26 29044427
2022 C2CD6 regulates targeting and organization of the CatSper calcium channel complex in sperm flagella. Development (Cambridge, England) 24 34919125
2021 [Ca2+]i oscillations in human sperm are triggered in the flagellum by membrane potential-sensitive activity of CatSper. Human reproduction (Oxford, England) 23 33305795
2020 Pentachlorophenol inhibits CatSper function to compromise progesterone's action on human sperm. Chemosphere 23 32622245
2021 Pharmacological Inactivation of CatSper Blocks Sperm Fertilizing Ability Independently of the Capacitation Status of the Cells: Implications for Non-hormonal Contraception. Frontiers in cell and developmental biology 22 34295893
2021 Conserved Mechanism of Bicarbonate-Induced Sensitization of CatSper Channels in Human and Mouse Sperm. Frontiers in cell and developmental biology 22 34650979
2018 Effects of pH manipulation, CatSper stimulation and Ca2+-store mobilization on [Ca2+]i and behaviour of human sperm. Human reproduction (Oxford, England) 22 30239776
2017 Chromatin Protamination and Catsper Expression in Spermatozoa Predict Clinical Outcomes after Assisted Reproduction Programs. Scientific reports 21 29123209
2011 Immunization of male mice with B-cell epitopes in transmembrane domains of CatSper1 inhibits fertility. Fertility and sterility 21 22196715
2006 The expression and significance of CATSPER1 in human testis and ejaculated spermatozoa. Asian journal of andrology 21 16625279
2017 Network model predicts that CatSper is the main Ca2+ channel in the regulation of sea urchin sperm motility. Scientific reports 20 28652586
2023 A CUG-initiated CATSPERθ functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking. Proceedings of the National Academy of Sciences of the United States of America 19 37725640
2021 Cdc42 localized in the CatSper signaling complex regulates cAMP-dependent pathways in mouse sperm. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19 34224609
2013 Effects of Vitamin-E treatment on CatSper genes expression and sperm quality in the testis of the aging mouse. Iranian journal of reproductive medicine 19 24639725
2012 Down-regulation of CatSper1 channel in epididymal spermatozoa contributes to the pathogenesis of asthenozoospermia, whereas up-regulation of the channel by Sheng-Jing-San treatment improves the sperm motility of asthenozoospermia in rats. Fertility and sterility 19 23148924
2021 CRISP2, CATSPER1 and PATE1 Expression in Human Asthenozoospermic Semen. Cells 18 34440724
2019 Expression Analysis of the CRISP2, CATSPER1, PATE1 and SEMG1 in the Sperm of Men with Idiopathic Asthenozoospermia. Journal of reproduction & infertility 18 31058050
2018 Inhibition of the CatSper Channel and NOX5 Enzyme Activity Affects the Functions of the Progesterone-Stimulated Human Sperm. Iranian journal of medical sciences 18 29398748
2017 CCR6 is required for ligand-induced CatSper activation in human sperm. Oncotarget 18 29207656
2019 Inhibition of CatSper and Hv1 Channels and NOX5 Enzyme Affect Progesterone-Induced Increase of Intracellular Calcium Concentration and ROS Generation in Human Sperm. Iranian journal of medical sciences 17 30936599
2014 Panax ginseng induces the expression of CatSper genes and sperm hyperactivation. Asian journal of andrology 17 24969054
2021 The Action of Reproductive Fluids and Contained Steroids, Prostaglandins, and Zn2+ on CatSper Ca2+ Channels in Human Sperm. Frontiers in cell and developmental biology 16 34381781
2019 The effect of clomiphene citrate and human chorionic gonadotropin on the expression of CatSper1, CatSper2, LHCGR, and SF1 genes, as well as the structural changes in testicular tissue of adult rats. Molecular reproduction and development 15 31041823
2017 Cryopreservation of cynomolgus macaque (Macaca fascicularis) sperm with glycerol and ethylene glycol, and its effect on sperm-specific ion channels - CatSper and Hv1. Theriogenology 15 28806626
2015 Analysis of the correlation of CATSPER single nucleotide polymorphisms (SNPs) with idiopathic asthenospermia. Journal of assisted reproduction and genetics 15 26354096
2022 SOX11-dependent CATSPER1 expression controls colon cancer cell growth through regulation the PI3K/AKT signaling pathway. Genes & genomics 14 35305240
2020 Does the Pre-Ovulatory Pig Oviduct Rule Sperm Capacitation In Vivo Mediating Transcriptomics of Catsper Channels? International journal of molecular sciences 14 32155986
2018 Alteration in CatSper1 and 2 genes expression, sperm parameters and testis histology in varicocelized rats. International journal of reproductive biomedicine 14 29766149
2018 Assessment of sperm morphology, chromatin integrity, and catSper genes expression in hypothyroid mice. Acta biologica Hungarica 14 30257580
2015 Construction of a catsper1 DNA vaccine and its antifertility effect on male mice. PloS one 14 25993432
2006 Association of Catsper1 or -2 with Ca(v)3.3 leads to suppression of T-type calcium channel activity. The Journal of biological chemistry 14 16740636
2024 Both protein and non-protein components in extracellular vesicles of human seminal plasma improve human sperm function via CatSper-mediated calcium signaling. Human reproduction (Oxford, England) 13 38335261
2022 In vitro investigation of endocrine disrupting effects of pesticides on Ca2+-signaling in human sperm cells through actions on the sperm-specific and steroid-activated CatSper Ca2+-channel. Environment international 13 35853389
2021 Molecular Evolution of CatSper in Mammals and Function of Sperm Hyperactivation in Gray Short-Tailed Opossum. Cells 13 33946695
2023 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 12 36743410
2022 Prevention of Testicular Damage by Indole Derivative MMINA via Upregulated StAR and CatSper Channels with Coincident Suppression of Oxidative Stress and Inflammation: In Silico and In Vivo Validation. Antioxidants (Basel, Switzerland) 12 36290786
2014 Correlation between expression of CatSper family and sperm profiles in the adult mouse testis following Iranian Kerack abuse. Andrology 12 24619711
2013 Molecular cloning and analysis of the Catsper1 gene promoter. Molecular human reproduction 12 23313885
2022 Human sperm cells can form paracetamol metabolite AM404 that directly interferes with sperm calcium signalling and function through a CatSper-dependent mechanism. Human reproduction (Oxford, England) 11 35259261
2020 Modular analysis of the control of flagellar Ca2+-spike trains produced by CatSper and CaV channels in sea urchin sperm. PLoS computational biology 11 32119665
2019 The CatSper channel is present and plays a key role in sperm motility of the Atlantic salmon (Salmo salar). Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 11 31841710
2018 Down-regulation of CatSper 1 and CatSper 2 genes by lead and mercury. Environmental toxicology and pharmacology 11 29549816
2017 Catsper1 promoter is bidirectional and regulates the expression of a novel lncRNA. Scientific reports 11 29042633
2022 Bicarbonate-Triggered In Vitro Capacitation of Boar Spermatozoa Conveys an Increased Relative Abundance of the Canonical Transient Receptor Potential Cation (TRPC) Channels 3, 4, 6 and 7 and of CatSper-γ Subunit mRNA Transcripts. Animals : an open access journal from MDPI 10 35454259
2021 Finasteride interferes with prostaglandin-induced CatSper signalling in human sperm. Reproduction (Cambridge, England) 10 33729179
2018 Human CATSPER1 Promoter Is Regulated by CREB1 and CREMτ Transcriptional Factors In Vitro. Archives of medical research 10 30017233
2011 Molecular cloning, spatial and temporal expression analysis of CatSper genes in the Chinese Meishan pigs. Reproductive biology and endocrinology : RB&E 10 21970684
2023 CatSper mediates not only chemotactic behavior but also the motility of ascidian sperm. Frontiers in cell and developmental biology 9 38020915
2021 TET1 mediated male reproductive toxicity induced by Bisphenol A through Catsper-Ca2+ signaling pathway. Environmental pollution (Barking, Essex : 1987) 9 34953956
2019 Effect of selenium and pentoxifylline on expression of CATSPER1 and 2 genes and FSH/LH levels in treated mice by dexamethasone. Andrologia 9 30983026
2012 Sperm are promiscuous and CatSper is to blame…. The EMBO journal 9 22415366
2024 Flagellar pH homeostasis mediated by Na+/H+ exchangers regulates human sperm functions through coupling with CatSper and KSper activation. Human reproduction (Oxford, England) 8 38366201
2024 Environmental pollutants and male infertility: Effects on CatSper. Ecotoxicology and environmental safety 8 38653022
2022 CatSper and its CaM-like Ca2+ sensor EFCAB9 are necessary for the path chirality of sperm. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 8 35438819
2021 CatSper channels in sea urchin sperm. Cell calcium 8 34509139
2014 Structural evolution of CatSper1 in rodents is influenced by sperm competition, with effects on sperm swimming velocity. BMC evolutionary biology 8 24884901
2008 CatSper genes expression, semen characteristics and histology of testes in the contusive spinal cord-injured mice model. Spinal cord 8 18607386
2022 Association of CATSPER1, SPATA16 and TEX11 genes polymorphism with idiopathic azoospermia and oligospermia risk in Iranian population. BMC medical genomics 7 35248021
2016 Cd(2+) sensitivity and permeability of a low voltage-activated Ca(2+) channel with CatSper-like selectivity filter. Cell calcium 7 27134080
2015 The Fungal Sexual Pheromone Sirenin Activates the Human CatSper Channel Complex. ACS chemical biology 7 26674547
2024 Sperm hyperactivation and the CatSper channel: current understanding and future contribution of domestic animals. Journal of animal science and technology 6 38975583