2019
Leukocyte Cytoskeleton Polarization Is Initiated by Plasma Membrane Curvature from Cell Attachment
Ren C, Yuan Q, Braun M, Zhang X, Petri B, Zhang J, Kim D, Guez-Haddad J, Xue W, Pan W, Fan R, Kubes P, Sun Z, Opatowsky Y, Polleux F, Karatekin E, Tang W, Wu D. Leukocyte Cytoskeleton Polarization Is Initiated by Plasma Membrane Curvature from Cell Attachment. Developmental Cell 2019, 49: 206-219.e7. PMID: 30930167, PMCID: PMC6482112, DOI: 10.1016/j.devcel.2019.02.023.Peer-Reviewed Original ResearchActinsAnimalsCell AdhesionCell MembraneCell MovementCell PolarityCell-Matrix JunctionsCytoskeletonEndotheliumFemaleGTPase-Activating ProteinsHEK293 CellsHumansLeukocytesMaleMiceMice, Inbred C57BLMice, KnockoutMinor Histocompatibility AntigensMyosin Light ChainsNeutrophilsPhosphatidylinositol PhosphatesPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Signal Transduction
2018
Polycystin-1 regulates bone development through an interaction with the transcriptional coactivator TAZ
Merrick D, Mistry K, Wu J, Gresko N, Baggs JE, Hogenesch JB, Sun Z, Caplan MJ. Polycystin-1 regulates bone development through an interaction with the transcriptional coactivator TAZ. Human Molecular Genetics 2018, 28: 16-30. PMID: 30215740, PMCID: PMC6298236, DOI: 10.1093/hmg/ddy322.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBone DevelopmentCell DifferentiationE1A-Associated p300 ProteinGene Expression RegulationGenes, RegulatorHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsKidneyModels, AnimalMorpholinosOsteoblastsOsteogenesisPolycystic Kidney, Autosomal DominantTrans-ActivatorsTranscription FactorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTRPP Cation ChannelsZebrafishZebrafish ProteinsConceptsC-terminal tailCurly tail phenotypePolycystin-1Tail phenotypeTranscriptional coactivator TAZMessenger RNARunx2 transcriptional activityBone developmentTranscription factor Runx2Co-regulatory proteinsPkd1 mutant miceEssential coactivatorTranscriptional pathwaysTranscriptional activityOsteoblast differentiationKey mechanistic linkTAZPhysiological functionsPKD1 geneMechanistic linkRunx2MorpholinoPhenotypeMutant miceAutosomal dominant polycystic kidney disease
2017
Palmitoylation of the ciliary GTPase ARL13b is necessary for its stability and its role in cilia formation
Roy K, Jerman S, Jozsef L, McNamara T, Onyekaba G, Sun Z, Marin EP. Palmitoylation of the ciliary GTPase ARL13b is necessary for its stability and its role in cilia formation. Journal Of Biological Chemistry 2017, 292: 17703-17717. PMID: 28848045, PMCID: PMC5663873, DOI: 10.1074/jbc.m117.792937.Peer-Reviewed Original ResearchConceptsPost-translational attachmentMost mammalian cellsCiliary GTPase Arl13bCilia localizationProtein palmitoylationCiliary proteinsCilia proteinsProtein localizationCilia formationMammalian cellsCilia functionPalmitoylationPrimary ciliaPlasma membraneCilia resorptionArl13bFunctional importanceMyristoylationCiliaCritical roleProteinMouse kidneyLocalizationDepalmitoylationCellsX-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
Olcese C, Patel MP, Shoemark A, Kiviluoto S, Legendre M, Williams HJ, Vaughan CK, Hayward J, Goldenberg A, Emes RD, Munye MM, Dyer L, Cahill T, Bevillard J, Gehrig C, Guipponi M, Chantot S, Duquesnoy P, Thomas L, Jeanson L, Copin B, Tamalet A, Thauvin-Robinet C, Papon J, Garin A, Pin I, Vera G, Aurora P, Fassad MR, Jenkins L, Boustred C, Cullup T, Dixon M, Onoufriadis A, Bush A, Chung EM, Antonarakis SE, Loebinger MR, Wilson R, Armengot M, Escudier E, Hogg C, Amselem S, Sun Z, Bartoloni L, Blouin J, Mitchison H. X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3. Nature Communications 2017, 8: 14279. PMID: 28176794, PMCID: PMC5309803, DOI: 10.1038/ncomms14279.Peer-Reviewed Original ResearchAdolescentAdultAnimalsApoptosis Regulatory ProteinsAxonemal DyneinsAxonemeChildChild, PreschoolCiliaCytoplasmDisease Models, AnimalExome SequencingFemaleGenes, X-LinkedGenetic Diseases, X-LinkedHEK293 CellsHSP90 Heat-Shock ProteinsHumansInfant, NewbornIntracellular Signaling Peptides and ProteinsKartagener SyndromeMaleMicroscopy, Electron, TransmissionMicrotubule ProteinsMolecular ChaperonesPedigreePhylogenyPoint MutationProtein FoldingSequence AlignmentSequence DeletionSperm MotilityZebrafishChapter Two Using Zebrafish to Study Kidney Development and Disease
Jerman S, Sun Z. Chapter Two Using Zebrafish to Study Kidney Development and Disease. Current Topics In Developmental Biology 2017, 124: 41-79. PMID: 28335864, DOI: 10.1016/bs.ctdb.2016.11.008.Peer-Reviewed Original ResearchConceptsKidney developmentAttractive vertebrate modelShares significant similarityRenal developmental defectsVertebrate modelVertebrate kidneyDanio rerioZebrafish modelSignificant similarityZebrafishDevelopmental defectsWater homeostasisRepair processFunctional unitsVertebratesRerioPowerful toolHuman patientsInvaluable informationSimilarityProfound potentialChapter TwoHomeostasisPromising modelDevelopment
2016
Deletion of ADP Ribosylation Factor-Like GTPase 13B Leads to Kidney Cysts
Li Y, Tian X, Ma M, Jerman S, Kong S, Somlo S, Sun Z. Deletion of ADP Ribosylation Factor-Like GTPase 13B Leads to Kidney Cysts. Journal Of The American Society Of Nephrology 2016, 27: 3628-3638. PMID: 27153923, PMCID: PMC5118478, DOI: 10.1681/asn.2015091004.Peer-Reviewed Original ResearchConceptsSevere patterning defectsMultiple model organismsSmall GTPase essentialDefective hedgehog signalingCystic kidneysNumber of phenotypesKidney cyst formationKidney cystsJoubert syndromeGTPase essentialZebrafish leadsPatterning defectsBiogenesis defectsModel organismsCilia biogenesisLoss of functionCyst progressionDefective ciliaHistone deacetylase inhibitorsHuman mutationsNull mutationHedgehog signalingHypomorphic natureRescue experimentsNeural tubeHypomorphic mutations identified in the candidate Leber congenital amaurosis gene CLUAP1
Soens ZT, Li Y, Zhao L, Eblimit A, Dharmat R, Li Y, Chen Y, Naqeeb M, Fajardo N, Lopez I, Sun Z, Koenekoop RK, Chen R. Hypomorphic mutations identified in the candidate Leber congenital amaurosis gene CLUAP1. Genetics In Medicine 2016, 18: 1044-1051. PMID: 26820066, PMCID: PMC4965339, DOI: 10.1038/gim.2015.205.Peer-Reviewed Original ResearchConceptsLeber congenital amaurosisLCA genesRescue experimentsEarly-onset formPhotoreceptor cell deathWhole-exome sequencingDysfunctional photoreceptorsRetinal disease genesCause of diseaseSystemic abnormalitiesLCA cohortMouse retinaRetinal degenerationHypomorphic mutationsCongenital amaurosisLCA patientsCilia-associated genesPhotoreceptor functionProband's mutationCell deathDiseaseProbandsSingle probandHuman diseasesCilia function
2015
Intraciliary Calcium Oscillations Initiate Vertebrate Left-Right Asymmetry
Yuan S, Zhao L, Brueckner M, Sun Z. Intraciliary Calcium Oscillations Initiate Vertebrate Left-Right Asymmetry. Current Biology 2015, 25: 556-567. PMID: 25660539, PMCID: PMC4469357, DOI: 10.1016/j.cub.2014.12.051.Peer-Reviewed Original ResearchConceptsLeft-right organizerLR developmentCiliary motilityVertebrate left–right asymmetryLeft-right signalingLive zebrafish embryosVertebrate developmentLeft-right asymmetryZebrafish embryosSensory ciliaPolycystin-2Signaling cascadesMolecular signalsMolecular mechanismsIntraciliary calciumCation channelsMotilityBilateral symmetryCalcium sinkCiliaCalcium oscillationsPKD2SignalingEmbryosExtracellular fluid
2014
IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet–Biedl syndrome
Aldahmesh MA, Li Y, Alhashem A, Anazi S, Alkuraya H, Hashem M, Awaji AA, Sogaty S, Alkharashi A, Alzahrani S, Al Hazzaa S, Xiong Y, Kong S, Sun Z, Alkuraya FS. IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet–Biedl syndrome. Human Molecular Genetics 2014, 23: 3307-3315. PMID: 24488770, PMCID: PMC4047285, DOI: 10.1093/hmg/ddu044.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceAnimalsBardet-Biedl SyndromeConsanguinityEvolution, MolecularExomeFemaleGenetic Predisposition to DiseaseHigh-Throughput Nucleotide SequencingHumansMaleModels, MolecularMonomeric GTP-Binding ProteinsPedigreePoint MutationSaudi ArabiaSequence AlignmentZebrafishConceptsBardet-Biedl syndromeBBS genesNovel BBS geneIntraflagellar transport genesAutosomal recessive ciliopathyIFT particlesProtein complexesTransport genesMembrane proteinsFunctional validationGenetic complexityRecessive ciliopathyHuman geneticsGenesIFT27Genetic heterogeneityConsanguineous familyBBS casesBBSomeZebrafishCiliopathiesGeneticsProteinCiliaFirst time
2013
Expanding Horizons: Ciliary Proteins Reach Beyond Cilia
Yuan S, Sun Z. Expanding Horizons: Ciliary Proteins Reach Beyond Cilia. Annual Review Of Genetics 2013, 47: 353-376. PMID: 24016188, PMCID: PMC5703194, DOI: 10.1146/annurev-genet-111212-133243.Peer-Reviewed Original ResearchMeSH KeywordsAbnormalities, MultipleAnimalsBardet-Biedl SyndromeCell MovementCerebellar DiseasesCerebellumCiliaCiliary Motility DisordersDisease Models, AnimalDNA DamageDNA RepairEncephaloceleEye AbnormalitiesFlagellaHeterotaxy SyndromeHomeostasisHumansKidney Diseases, CysticMolecular Motor ProteinsNervous SystemPolycystic Kidney DiseasesPolycystic Kidney, Autosomal DominantPolycystic Kidney, Autosomal RecessiveRetinaRetinitis PigmentosaZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with LRRC6
Zariwala MA, Gee HY, Kurkowiak M, Al-Mutairi DA, Leigh MW, Hurd TW, Hjeij R, Dell SD, Chaki M, Dougherty GW, Adan M, Spear PC, Esteve-Rudd J, Loges NT, Rosenfeld M, Diaz KA, Olbrich H, Wolf WE, Sheridan E, Batten TF, Halbritter J, Porath JD, Kohl S, Lovric S, Hwang DY, Pittman JE, Burns KA, Ferkol TW, Sagel SD, Olivier KN, Morgan LC, Werner C, Raidt J, Pennekamp P, Sun Z, Zhou W, Airik R, Natarajan S, Allen SJ, Amirav I, Wieczorek D, Landwehr K, Nielsen K, Schwerk N, Sertic J, Köhler G, Washburn J, Levy S, Fan S, Koerner-Rettberg C, Amselem S, Williams DS, Mitchell BJ, Drummond IA, Otto EA, Omran H, Knowles MR, Hildebrandt F. ZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with LRRC6. American Journal Of Human Genetics 2013, 93: 336-345. PMID: 23891469, PMCID: PMC3738827, DOI: 10.1016/j.ajhg.2013.06.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantigensAxonemal DyneinsBiomarkersCell Cycle ProteinsCiliaCytoskeletal ProteinsExomeGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansKartagener SyndromeMaleMicrotubule-Associated ProteinsMutationPedigreeProtein BindingProtein Structure, TertiaryProteinsRatsRespiratory SystemTumor Suppressor ProteinsXenopus laevisZebrafishConceptsCytoplasmic protein complexesMotile ciliary functionC-terminal domainWhole-exome resequencingProtein complexesHuman primary ciliary dyskinesiaZMYND10LRRC6Motile ciliaHigh-throughput mutation analysisOtolith defectsPrimary ciliary dyskinesiaCiliary functionMutationsCS domainBiallelic mutationsKnockdownCystic kidneysMutation analysisCiliaCiliary dyskinesiaSAS6ResequencingZebrafishCiliogenesisPolycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy
Paavola J, Schliffke S, Rossetti S, Kuo I, Yuan S, Sun Z, Harris PC, Torres VE, Ehrlich BE. Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy. Journal Of Molecular And Cellular Cardiology 2013, 58: 199-208. PMID: 23376035, PMCID: PMC3636149, DOI: 10.1016/j.yjmcc.2013.01.015.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseHeart failureCalcium cyclingCardiac functionProteins polycystin-1Low cardiac outputHuman autosomal dominant polycystic kidney diseaseDominant polycystic kidney diseaseImpaired calcium cyclingIntracellular calcium cyclingCause of mortalityIntracellular calcium signalingPolycystic kidney diseasePolycystin-2Intracellular calcium channelsAtrioventricular blockCardiac outputKidney diseaseADPKD patientsCardiovascular diseaseRenal epithelial cellsCalcium channelsDilated CardiomyopathyPKD2 mutationsEpithelial cells
2012
Target-of-rapamycin complex 1 (Torc1) signaling modulates cilia size and function through protein synthesis regulation
Yuan S, Li J, Diener DR, Choma MA, Rosenbaum JL, Sun Z. Target-of-rapamycin complex 1 (Torc1) signaling modulates cilia size and function through protein synthesis regulation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 2021-2026. PMID: 22308353, PMCID: PMC3277533, DOI: 10.1073/pnas.1112834109.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody PatterningCiliaEvolution, MolecularGene Knockdown TechniquesGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansMovementOrgan SizeProtein BiosynthesisRheologyRibosomal Protein S6 KinasesSignal TransductionTranscription FactorsTuberous Sclerosis Complex 1 ProteinTumor Suppressor ProteinsZebrafishZebrafish ProteinsConceptsCilia lengthRibosomal protein S6 kinase 1Protein S6 kinase 1Protein synthesisLeft-right body asymmetryProtein synthesis regulationS6 kinase 1Vertebrate developmentTOR pathwayCilium sizeZebrafish developmentCilia assemblyTreatment of embryosDownstream substratesCilia morphologyEnvironmental cuesSynthesis regulationFluid flow generationKinase 1Cellular antennaHuman disordersCilia motilityUpstream inhibitorProper functionCiliary function
2011
The γ-Secretase Cleavage Product of Polycystin-1 Regulates TCF and CHOP-Mediated Transcriptional Activation through a p300-Dependent Mechanism
Merrick D, Chapin H, Baggs JE, Yu Z, Somlo S, Sun Z, Hogenesch JB, Caplan MJ. The γ-Secretase Cleavage Product of Polycystin-1 Regulates TCF and CHOP-Mediated Transcriptional Activation through a p300-Dependent Mechanism. Developmental Cell 2011, 22: 197-210. PMID: 22178500, PMCID: PMC3264829, DOI: 10.1016/j.devcel.2011.10.028.Peer-Reviewed Original ResearchMeSH KeywordsAmyloid Precursor Protein SecretasesAnimalsApoptosisCell ProliferationCells, CulturedCystsEmbryo, NonmammalianHumansImmunoblottingImmunoprecipitationKidneyP300-CBP Transcription FactorsPhenotypePolycystic Kidney, Autosomal DominantTCF Transcription FactorsTranscription Factor CHOPTranscriptional ActivationTRPP Cation ChannelsWnt Signaling PathwayZebrafishConceptsCarboxy-terminal tailPolycystin-1P300-dependent mechanismTranscription factor TCFTranscriptional coactivator p300Cultured renal epithelial cellsΓ-secretase-mediated cleavageAutosomal dominant polycystic kidney diseaseRenal epithelial cellsTranscriptional activationZebrafish embryosCoactivator p300Γ-secretase activityNormal growth ratePKD1 expressionNull cellsProtein fragmentsCyst formationΓ-secretase inhibitionCHOP pathwayApoptosisEpithelial cellsCleavage productsPolycystic kidney diseaseExpressionQilin Is Essential for Cilia Assembly and Normal Kidney Development in Zebrafish
Li J, Sun Z. Qilin Is Essential for Cilia Assembly and Normal Kidney Development in Zebrafish. PLOS ONE 2011, 6: e27365. PMID: 22102889, PMCID: PMC3216947, DOI: 10.1371/journal.pone.0027365.Peer-Reviewed Original ResearchConceptsCilia assemblyIFT complex B proteinsKidney developmentForward genetic screenCoiled-coil domainEssential roleKidney cystsNormal kidney developmentGenetic screenMutant phenotypeVestigial organelleNovel genesPolycystic kidney diseaseCilia formationDeletion analysisB geneB proteinB mutantsGenetic analysisMeckel-Gruber syndromeN-terminusFunctional analysisRescue experimentsZebrafishHuman diseasesA cell‐based screen for inhibitors of flagella‐driven motility in Chlamydomonas reveals a novel modulator of ciliary length and retrograde actin flow
Engel BD, Ishikawa H, Feldman JL, Wilson CW, Chuang P, Snedecor J, Williams J, Sun Z, Marshall WF. A cell‐based screen for inhibitors of flagella‐driven motility in Chlamydomonas reveals a novel modulator of ciliary length and retrograde actin flow. Cytoskeleton 2011, 68: 188-203. PMID: 21360831, DOI: 10.1002/cm.20504.Peer-Reviewed Original ResearchConceptsRetrograde actin flowActin flowUnicellular green alga Chlamydomonas reinhardtiiGreen alga Chlamydomonas reinhardtiiFlagella-driven motilityDrosophila S2 cellsAlga Chlamydomonas reinhardtiiTraditional genetic methodsChemical biology toolkitCell-based screenHuman disease symptomsLength of ciliaCiliary assemblyFlagellar paralysisS2 cellsIntraflagellar transportGenetic toolsFlagellar shorteningChlamydomonas reinhardtiiMammalian cellsSensory organellesGenetic methodsCiliary lengthCiliary defectsNovel modulatorChapter 3 Analysis of Cilia Structure and Function in Zebrafish
Malicki J, Avanesov A, Li J, Yuan S, Sun Z. Chapter 3 Analysis of Cilia Structure and Function in Zebrafish. Methods In Cell Biology 2011, 101: 39-74. PMID: 21550439, DOI: 10.1016/b978-0-12-387036-0.00003-7.Peer-Reviewed Original ResearchConceptsExcellent vertebrate model systemVertebrate model systemNormal embryonic developmentCell surface protrusionsCilia biologyGenetic accessibilityVertebrate cellsLimb morphogenesisCilia formationImportant organellesEmbryonic developmentLarval organsLeft-right asymmetryCilia structureDistribution of ciliaNephric ductZebrafishCiliary malfunctionVariety of processesPhotoreceptor cellsSensory cellsKidney cystsCiliaModel systemChapter 3 Analysis
2010
Cilia in cell signaling and human disorders
Duldulao NA, Li J, Sun Z. Cilia in cell signaling and human disorders. Protein & Cell 2010, 1: 726-736. PMID: 21203914, PMCID: PMC4875200, DOI: 10.1007/s13238-010-0098-7.Peer-Reviewed Original ResearchConceptsRole of ciliaUnrelated human diseasesMulticellular organismsVestigial organelleCell signalingCellular organellesNormal organogenesisHuman disordersHuman diseasesCiliaKidney cystsOrganellesSensory roleNeural tube defectsCiliogenesisOrganogenesisDevelopmental disordersMotileOrganismsSignalingTube defectsRoleDefects
2009
Cilia localization is essential for in vivo functions of the Joubert syndrome protein Arl13b/Scorpion
Duldulao NA, Lee S, Sun Z. Cilia localization is essential for in vivo functions of the Joubert syndrome protein Arl13b/Scorpion. Development 2009, 136: 4033-4042. PMID: 19906870, PMCID: PMC2778746, DOI: 10.1242/dev.036350.Peer-Reviewed Original ResearchConceptsCilia formationVivo functionJoubert syndromeSeries of deletionsSonic hedgehog (Shh) signalingCilia localizationCiliary localizationNull mutantsPoint mutantsGene productsHedgehog signalingArl13bCiliary defectsMutantsKidney ductsZebrafishCiliaAutosomal recessive disorderAbnormal ultrastructureScorpionsRecessive disorderLocalizationRecent studiesKnockdownSignaling