2021
Structural insights into the cause of human RSPH4A primary ciliary dyskinesia
Zhao Y, Pinskey J, Lin J, Yin W, Sears P, Daniels L, Zariwala M, Knowles M, Ostrowski L, Nicastro D. Structural insights into the cause of human RSPH4A primary ciliary dyskinesia. Molecular Biology Of The Cell 2021, 32: 1202-1209. PMID: 33852348, PMCID: PMC8351563, DOI: 10.1091/mbc.e20-12-0806.Peer-Reviewed Original ResearchConceptsStructural basisCryo-electron tomographyRadial spokesCentral pair complexUnderlying structural basisAxonemal repeatEukaryotic organellesArch domainThree-dimensional structureSubtomogram averagingOrgan positioningCell motilityStructural insightsPrimary ciliary dyskinesiaCiliaHuman ciliaHuman respiratory ciliaRS1Primary defectStructure determinationCiliary dyskinesiaHuman healthOrganellesFlagellaRepeats
2019
FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
Lin J, Le TV, Augspurger K, Tritschler D, Bower R, Fu G, Perrone C, O’Toole E, Mills KV, Dymek E, Smith E, Nicastro D, Porter ME. FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia. Molecular Biology Of The Cell 2019, 30: 2659-2680. PMID: 31483737, PMCID: PMC6761771, DOI: 10.1091/mbc.e19-07-0367.Peer-Reviewed Original ResearchConceptsInner dynein armsRegulatory complexCryo-electron tomographyInner arm dyneinsCiliary motilityMultiple dynein motorsPrecise spatial organizationAxonemal repeatDocking factorUnique binding siteWD repeatsDynein assemblyAssembly factorsDomain proteinsRegulatory hubDynein complexDynein isoformsDynein subunitsInsertional mutagenesisNew lociRegulatory proteinsDynein motorsDifferent dyneinsDoublet microtubulesTransport factorsPACRG and FAP20 form the inner junction of axonemal doublet microtubules and regulate ciliary motility
Dymek EE, Lin J, Fu G, Porter ME, Nicastro D, Smith EF. PACRG and FAP20 form the inner junction of axonemal doublet microtubules and regulate ciliary motility. Molecular Biology Of The Cell 2019, 30: 1805-1816. PMID: 31116684, PMCID: PMC6727744, DOI: 10.1091/mbc.e19-01-0063.Peer-Reviewed Original ResearchConceptsDoublet microtubulesAxonemal doublet microtubulesCryo-electron tomographyCiliary doublet microtubulesInner junctionCiliary assemblyCoordinated ciliary beatingFAP20Ciliary componentsMotility defectsCiliary beatingPACRGMotile ciliaFunctional studiesMutant axonemesMicrotubulesB-tubuleCiliary motilityEssential roleStructural studiesAssemblyMotilityChlamydomonasMutantsAxoneme
2018
Asymmetric distribution and spatial switching of dynein activity generates ciliary motility
Lin J, Nicastro D. Asymmetric distribution and spatial switching of dynein activity generates ciliary motility. Science 2018, 360 PMID: 29700238, PMCID: PMC6640125, DOI: 10.1126/science.aar1968.Peer-Reviewed Original ResearchConceptsDynein activitySea urchin sperm cellsCryo-electron tomographyIndividual dyneinsDynein isoformsAsymmetric distributionMotile ciliaDyneinFlagellaHypothesis positsSperm cellsSmall populationCiliary motilityFlagellar bendingCoordinated activityActive stateMotilityActivity stateOrganellesIsoformsCiliaActivity
2014
Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia
Lin J, Yin W, Smith MC, Song K, Leigh MW, Zariwala MA, Knowles MR, Ostrowski LE, Nicastro D. Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia. Nature Communications 2014, 5: 5727. PMID: 25473808, PMCID: PMC4267722, DOI: 10.1038/ncomms6727.Peer-Reviewed Original ResearchConceptsCryo-electron tomographyNative 3D structureNormal human developmentDistant speciesHuman ciliaCilia structurePCD phenotypeCilia dysfunctionHuman diseasesNative structurePrimary ciliary dyskinesiaRadial spokesCiliaEssential roleFunctional heterogeneityHuman respiratory ciliaUnprecedented detailPrimary defectCiliary dyskinesiaUnknown primary defect
2012
Conserved structural motifs in the central pair complex of eukaryotic flagella
Carbajal‐González B, Heuser T, Fu X, Lin J, Smith BW, Mitchell DR, Nicastro D. Conserved structural motifs in the central pair complex of eukaryotic flagella. Cytoskeleton 2012, 70: 101-120. PMID: 23281266, PMCID: PMC3914236, DOI: 10.1002/cm.21094.Peer-Reviewed Original ResearchConceptsCentral pair complexCilia/flagellaRemarkable structural conservationGreen alga ChlamydomonasConserved Structural MotifCryo-electron tomographyOrganism-specific differencesEukaryotic cellsSea urchin StrongylocentrotusEvolutionary distanceStructural conservationAlga ChlamydomonasThree-dimensional structureSubtomogram averagingEukaryotic flagellaAxonemal dyneinsPrecise regulationInner proteinsMotility regulatorHair-like appendagesSinglet microtubulesChlamydomonasHuman diseasesDoublet microtubulesFlagellaThe CSC connects three major axonemal complexes involved in dynein regulation
Heuser T, Dymek EE, Lin J, Smith EF, Nicastro D. The CSC connects three major axonemal complexes involved in dynein regulation. Molecular Biology Of The Cell 2012, 23: 3143-3155. PMID: 22740634, PMCID: PMC3418309, DOI: 10.1091/mbc.e12-05-0357.Peer-Reviewed Original ResearchConceptsNexin-dynein regulatory complexDynein regulationRadial spokesAxonemal complexCryo-electron tomographyWild-type motilityRegulatory complexFlagellar motilityDynein motorsChlamydomonas flagellaMotile ciliaStable assemblyFlagellaDifferent functionsRegulationRS1ComplexesMotilityStructural heterogeneityRS2Human healthImportant roleOrganellesHomologuesCSC