Featured Publications
Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome
Bruel A, Ganga A, Nosková L, Valenzuela I, Martinovic J, Duffourd Y, Zikánová M, Majer F, Kmoch S, Mohler M, Sun J, Sweeney L, Martínez-Gil N, Thauvin-Robinet C, Breslow D. Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome. Human Molecular Genetics 2023, 32: 2822-2831. PMID: 37384395, PMCID: PMC10481091, DOI: 10.1093/hmg/ddad109.Peer-Reviewed Original ResearchConceptsCilia assemblyCiliary membrane formationIntracellular ciliogenesis pathwayPrimary cilia assemblyBi-allelic missense variantsRab proteinsRab GTPaseCiliary proteinsSmall GTPaseNascent ciliaMother centriolePrimary ciliaC-terminusProtein productsPathogenic variantsRab34Cell typesFunctional impactMissense variantsGTPaseStrong lossCiliogenesisSignificant defectsGenesKey mediatorRab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway
Ganga AK, Kennedy MC, Oguchi ME, Gray S, Oliver KE, Knight TA, De La Cruz EM, Homma Y, Fukuda M, Breslow DK. Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway. Current Biology 2021, 31: 2895-2905.e7. PMID: 33989527, PMCID: PMC8282722, DOI: 10.1016/j.cub.2021.04.075.Peer-Reviewed Original ResearchConceptsIntracellular pathwaysCiliary membrane biogenesisCiliary membrane formationIntracellular ciliogenesis pathwayMDCK cellsPolarized MDCK cellsDistinct molecular requirementsPrimary cilia formExtracellular pathwaysTissue-specific mannerCiliary pocketGTPase domainMembrane biogenesisDistinct functional propertiesCiliary vesiclesAssembly intermediatesCilia formSignal transductionGTP bindingMother centriolePrimary ciliaCiliogenesisDivergent residuesIntracellular ciliaRab34A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies
Breslow DK, Hoogendoorn S, Kopp AR, Morgens DW, Vu BK, Kennedy MC, Han K, Li A, Hess GT, Bassik MC, Chen JK, Nachury MV. A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies. Nature Genetics 2018, 50: 460-471. PMID: 29459677, PMCID: PMC5862771, DOI: 10.1038/s41588-018-0054-7.Peer-Reviewed Original ResearchConceptsFunctional genomic screensGenome-wide CRISPRCiliary functionHedgehog-responsive cellsCiliary signalingΕ-tubulinProtein complexesGenomic screenEmbryonic developmentGene disruptionPrimary ciliaΔ-tubulinNovel componentCiliopathiesCRISPRCiliary structureUnbiased toolHedgehogUnifying causeScreenGenesSignalingCiliaSystematic analysisPathwayAn in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier
Breslow DK, Koslover EF, Seydel F, Spakowitz AJ, Nachury MV. An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier. Journal Of Cell Biology 2013, 203: 129-147. PMID: 24100294, PMCID: PMC3798247, DOI: 10.1083/jcb.201212024.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsCell LineCell MembraneCell Membrane PermeabilityCiliaDiffusionMiceMicroscopy, FluorescenceMicroscopy, VideoModels, BiologicalMolecular WeightNuclear PoreProtein TransportProteinsRecombinant Fusion ProteinsReproducibility of ResultsTime FactorsTime-Lapse ImagingTransfectionConceptsNuclear pore complexCiliary diffusion barrierPore complexActin cytoskeletonMembrane proteinsActive transportPrimary ciliaPlasma membraneCiliary membraneSpecific proteinsLarge proteinsMechanistic basisPermeabilized cellsProteinCiliaAxon initial segmentMembraneCellsCytoskeletonInitial segmentEntryTransportAssaysVivoComplexes
2015
Chapter 11 Analysis of soluble protein entry into primary cilia using semipermeabilized cells
Breslow DK, Nachury MV. Chapter 11 Analysis of soluble protein entry into primary cilia using semipermeabilized cells. Methods In Cell Biology 2015, 127: 203-221. PMID: 25837393, PMCID: PMC4797650, DOI: 10.1016/bs.mcb.2014.12.006.BooksConceptsSemipermeabilized cellsProtein entriesPrimary ciliaCiliary diffusion barrierNuclear pore complexPrimary cilia functionPore complexMammalian cellsSignal transductionSpecialized compartmentsCilia functionPlasma membraneCiliary membraneIntact cellsExperimental perturbationsCell surfaceProtein exchangeCiliaVitro systemAxon initial segmentMechanistic analysisChapter 11 AnalysisUnique resourceCapture assayCells
2013
Single molecule imaging reveals a major role for diffusion in the exploration of ciliary space by signaling receptors
Ye F, Breslow DK, Koslover EF, Spakowitz AJ, Nelson WJ, Nachury MV. Single molecule imaging reveals a major role for diffusion in the exploration of ciliary space by signaling receptors. ELife 2013, 2: e00654. PMID: 23930224, PMCID: PMC3736543, DOI: 10.7554/elife.00654.Peer-Reviewed Original ResearchConceptsCiliary membrane proteinsIntraflagellar transportIFT trainsMembrane proteinsMembrane protein diffusionSingle-molecule imagingSomatostatin receptor 3Active transportPrimary ciliaCiliary membraneMolecule imagingProtein diffusionDynamic organizationDirectional movementReceptor 3ProteinCiliaPossible roleStatistical subtractionSingle moleculesMajor roleSmoothenedSMOSSTR3Diffusive behavior
2011
A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened
Seo S, Zhang Q, Bugge K, Breslow DK, Searby CC, Nachury MV, Sheffield VC. A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened. PLOS Genetics 2011, 7: e1002358. PMID: 22072986, PMCID: PMC3207910, DOI: 10.1371/journal.pgen.1002358.Peer-Reviewed Original ResearchConceptsCiliary traffickingBBS proteinsBardet-Biedl syndrome proteinsLeucine zipper transcriptionHedgehog signal transducerG protein-coupled receptorsProtein-coupled receptorsCiliary entryBBSome subunitsProtein traffickingSyndrome proteinProtein complexesCellular processesNovel proteinPrimary ciliaHedgehog signalingSignal transducerBBSomeImportant regulatorTraffickingLZTFL1Ciliary functionProteinBBS3CiliaPrimary Cilia: How to Keep the Riff-Raff in the Plasma Membrane
Breslow DK, Nachury MV. Primary Cilia: How to Keep the Riff-Raff in the Plasma Membrane. Current Biology 2011, 21: r434-r436. PMID: 21640903, DOI: 10.1016/j.cub.2011.04.039.Commentaries, Editorials and Letters