2023
LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility
Hwang J, Chai P, Nawaz S, Choi J, Lopez-Giraldez F, Hussain S, Bilguvar K, Mane S, Lifton R, Ahmad W, Zhang K, Chung J. LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility. ELife 2023, 12: rp90095. PMID: 38091523, PMCID: PMC10721216, DOI: 10.7554/elife.90095.Peer-Reviewed Original ResearchA CUG-initiated CATSPERθ functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking
Huang X, Miyata H, Wang H, Mori G, Iida-Norita R, Ikawa M, Percudani R, Chung J. 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 2023, 120: e2304409120. PMID: 37725640, PMCID: PMC10523455, DOI: 10.1073/pnas.2304409120.Peer-Reviewed Original ResearchConceptsChannel assemblySperm flagellaTransmembrane domain-containing proteinsSperm tail formationDomain-containing proteinsCatSper channel complexMale fertilityFlagellar traffickingMacromolecular complexesTail formationPhysiological roleSuccessful fertilizationCalcium signalingCatSper channelsFlagellaGenetic abrogationChannel complexNormal expressionDimer formationSpermatid cellsProteinCheckpointHyperactivated motilityAssemblyPotential role
2022
Selenoprotein TXNRD3 supports male fertility via the redox regulation of spermatogenesis
Dou Q, Turanov AA, Mariotti M, Hwang JY, Wang H, Lee SG, Paulo JA, Yim SH, Gygi SP, Chung JJ, Gladyshev VN. Selenoprotein TXNRD3 supports male fertility via the redox regulation of spermatogenesis. Journal Of Biological Chemistry 2022, 298: 102183. PMID: 35753352, PMCID: PMC9352919, DOI: 10.1016/j.jbc.2022.102183.Peer-Reviewed Original ResearchConceptsThioredoxin/glutathione reductaseThiol redox controlSperm quality controlThiol redox statusGene duplicationThiol oxidoreductasesRedox regulationProteomic analysisRedox controlGross phenotypeThioredoxin reductaseSperm maturationMovement phenotypesSperm cellsRedox statusMale reproductionKnockout animalsMale fertilityGlutathione reductaseCritical roleReductasePhenotypeTXNRD3Knockout miceSpermatogenesis3D structure and in situ arrangements of CatSper channel in the sperm flagellum
Zhao Y, Wang H, Wiesehoefer C, Shah NB, Reetz E, Hwang JY, Huang X, Wang TE, Lishko PV, Davies KM, Wennemuth G, Nicastro D, Chung JJ. 3D structure and in situ arrangements of CatSper channel in the sperm flagellum. Nature Communications 2022, 13: 3439. PMID: 35715406, PMCID: PMC9205950, DOI: 10.1038/s41467-022-31050-8.Peer-Reviewed Original ResearchConceptsCatSper complexSperm flagellaCryo-electron tomographyHigher-order organizationMammalian spermIntracellular domainStructural basisExtracellular domainTetrameric channelChannel CatSperSuccessful fertilizationFlagellar movementCatSper channelsChannel poreSitu mapSitu arrangementHuman sperm flagellumPrimary Ca2CatSperDimer formationFlagellaCentral roleSpermAtomic modelSperm motilityRedox regulation by TXNRD3 during epididymal maturation underlies capacitation-associated mitochondrial activity and sperm motility in mice
Wang H, Dou Q, Jeong KJ, Choi J, Gladyshev VN, Chung JJ. Redox regulation by TXNRD3 during epididymal maturation underlies capacitation-associated mitochondrial activity and sperm motility in mice. Journal Of Biological Chemistry 2022, 298: 102077. PMID: 35643315, PMCID: PMC9218152, DOI: 10.1016/j.jbc.2022.102077.Peer-Reviewed Original ResearchConceptsRedox regulationRedox homeostasisMolecular mechanismsSperm maturationMitochondrial sheath formationCell imaging analysisThioredoxin glutathione reductaseSperm developmentMammalian spermatozoaEpididymal transitMitochondrial ultrastructureMitochondrial activityRedox statusMale fertilityCapacitationHomeostasisMaturationRegulationMotilityFamily membersFertilizationSperm morphologySperm motilityMitochondriaBioenergeticsCatSper and its CaM‐like Ca2+ sensor EFCAB9 are necessary for the path chirality of sperm
Wiesehöfer C, Wiesehöfer M, Dankert JT, Chung J, von Ostau N, Singer BB, Wennemuth G. CatSper and its CaM‐like Ca2+ sensor EFCAB9 are necessary for the path chirality of sperm. The FASEB Journal 2022, 36: e22288. PMID: 35438819, PMCID: PMC9835897, DOI: 10.1096/fj.202101656rr.Peer-Reviewed Original ResearchConceptsNNC 55Exposure of spermMotility changesPharmacological inhibitionLateral head excursionCatSper activationIntracellular CaPhysiological stimuliCatSper channelsProtein 2Zona pellucida protein 2Zona pellucida glycoproteinsCapacitation stateCatSperHead excursionMouse spermPellucida glycoproteinsSpermSuccessful fertilizationMibefradilHigh frequencyC2cd6-encoded CatSperτ targets sperm calcium channel to Ca2+ signaling domains in the flagellar membrane
Hwang JY, Wang H, Lu Y, Ikawa M, Chung JJ. C2cd6-encoded CatSperτ targets sperm calcium channel to Ca2+ signaling domains in the flagellar membrane. Cell Reports 2022, 38: 110226. PMID: 34998468, PMCID: PMC8857959, DOI: 10.1016/j.celrep.2021.110226.Peer-Reviewed Original ResearchConceptsFlagellar membraneFlagellar membrane targetingC2 domain proteinsCatSper channelsCatSper channel complexMammalian sperm cellsSperm hyperactivated motilityMale fertilityMembrane targetingTrafficking machineryDomain proteinsLoss of functionHyperactivated motilitySpatiotemporal CaChannel assemblyMolecular mechanismsSperm cellsChannel complexFlagellaMotilityC2CD6MembraneCalcium channelsMachineryProtein
2020
3D in situ imaging of female reproductive tract reveals molecular signatures of fertilizing spermatozoa in mice
Ded L, Hwang JY, Miki K, Shi HF, Chung JJ. 3D in situ imaging of female reproductive tract reveals molecular signatures of fertilizing spermatozoa in mice. ELife 2020, 9: e62043. PMID: 33078708, PMCID: PMC7707823, DOI: 10.7554/elife.62043.Peer-Reviewed Original ResearchConceptsFemale reproductive tractFemale tractCalcium channel complexSitu molecular imagingReproductive tractMolecular insightsSuccessful fertilizationCatSper channelsMolecular signaturesSperm cellsSperm selectionChannel complexMouse spermatozoaFertilization siteSpermSperm migrationSpermatozoaMammalsPhosphorylationCatSper1ProteinSitu imagingAcrosomeUtero-tubal junctionSelection
2019
Dual Sensing of Physiologic pH and Calcium by EFCAB9 Regulates Sperm Motility
Hwang JY, Mannowetz N, Zhang Y, Everley RA, Gygi SP, Bewersdorf J, Lishko PV, Chung JJ. Dual Sensing of Physiologic pH and Calcium by EFCAB9 Regulates Sperm Motility. Cell 2019, 177: 1480-1494.e19. PMID: 31056283, PMCID: PMC8808721, DOI: 10.1016/j.cell.2019.03.047.Peer-Reviewed Original Research
2017
CatSperζ regulates the structural continuity of sperm Ca2+ signaling domains and is required for normal fertility
Chung JJ, Miki K, Kim D, Shim SH, Shi HF, Hwang JY, Cai X, Iseri Y, Zhuang X, Clapham DE. CatSperζ regulates the structural continuity of sperm Ca2+ signaling domains and is required for normal fertility. ELife 2017, 6: e23082. PMID: 28226241, PMCID: PMC5362262, DOI: 10.7554/elife.23082.Peer-Reviewed Original ResearchConceptsMammalian female reproductive tractSevere male subfertilityFemale reproductive tractIon channel complexNovel subunitCatSper complexEvolutionary adaptationMale subfertilityReproductive tractMouse spermSperm Ca2Normal fertilityTargeted disruptionSperm cellsFlagellaChannel complexFemale uterusSubunitsEpididymal spermatozoaSpermComplexesFertilizationSubfertilityUterusMice
2014
Structurally Distinct Ca2+ Signaling Domains of Sperm Flagella Orchestrate Tyrosine Phosphorylation and Motility
Chung JJ, Shim SH, Everley RA, Gygi SP, Zhuang X, Clapham DE. Structurally Distinct Ca2+ Signaling Domains of Sperm Flagella Orchestrate Tyrosine Phosphorylation and Motility. Cell 2014, 157: 808-822. PMID: 24813608, PMCID: PMC4032590, DOI: 10.1016/j.cell.2014.02.056.Peer-Reviewed Original ResearchConceptsTyrosine phosphorylationSperm-specific calcium channelsSpecific protein tyrosine phosphorylationProtein tyrosine phosphorylationSuper-resolution fluorescence microscopyMammalian flagellumUnique molecular phenotypeFlagellar switchHeterogeneous sperm populationsPaternal DNASignaling domainsMolecular phenotypesCatSper channelsMature eggsPhosphorylationFluorescence microscopyDistinct Ca2FlagellaAdaptive strategiesSperm populationCascade organizationSpermUniflagellateCalcium domainsPhosphoproteomics