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 ciliaRab34Mechanism and Regulation of Centriole and Cilium Biogenesis
Breslow DK, Holland AJ. Mechanism and Regulation of Centriole and Cilium Biogenesis. Annual Review Of Biochemistry 2019, 88: 1-34. PMID: 30601682, PMCID: PMC6588485, DOI: 10.1146/annurev-biochem-013118-111153.ChaptersConceptsInterphase microtubule cytoskeletonMicrotubule-based organellesBiogenesis of centriolesMost animal cellsCore of centrosomesFormation of ciliaNine-fold symmetryCilia biologyCilia biogenesisCellular signalingMicrotubule cytoskeletonAnimal cellsMitotic spindleBasal bodiesHuman diseasesCentriolesBiogenesisRegulatory controlCentral roleCiliaExciting avenuesCentrosomesCytoskeletonOrganellesSignalingA 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 analysisPathwayOrm family proteins mediate sphingolipid homeostasis
Breslow DK, Collins SR, Bodenmiller B, Aebersold R, Simons K, Shevchenko A, Ejsing CS, Weissman JS. Orm family proteins mediate sphingolipid homeostasis. Nature 2010, 463: 1048-1053. PMID: 20182505, PMCID: PMC2877384, DOI: 10.1038/nature08787.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAsthmaCell LineConserved SequenceFatty Acids, MonounsaturatedHeLa CellsHomeostasisHumansMolecular Sequence DataMultigene FamilyMultiprotein ComplexesPhosphoric Monoester HydrolasesPhosphorylationProtein BindingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSerine C-PalmitoyltransferaseSphingolipidsConceptsOrm proteinsSphingolipid homeostasisSphingolipid productionFunctional genomics approachSphingolipid metabolismGenomic approachesGene familyPhosphorylation sitesORM geneORMDL genesRate-limiting enzymeRegulatory pathwaysNegative regulatorGene expressionSphingolipid synthesisSerine palmitoyltransferaseEssential roleProteinCritical mediatorGenesHomeostasisStructural componentsMetabolismMisregulationSaccharomyces
2013
Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond
Breslow DK. Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond. Cold Spring Harbor Perspectives In Biology 2013, 5: a013326. PMID: 23545423, PMCID: PMC3683901, DOI: 10.1101/cshperspect.a013326.BooksConceptsSphingolipid homeostasisEndoplasmic reticulumEssential cellular rolesSphingolipid metabolismCritical regulatory sitePotent signaling moleculesCellular rolesFamily proteinsSphingolipid productionSignaling moleculesRegulatory sitesPhysiologic cuesBasic biochemistryComplex glycosphingolipidsMembrane functionHomeostasisDiverse groupSphingolipidsNew insightsReticulumMetabolic demandsDetailed understandingMetabolismStructural componentsInitial synthesis
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 functionProteinBBS3Cilia
2010
Membranes in Balance: Mechanisms of Sphingolipid Homeostasis
Breslow DK, Weissman JS. Membranes in Balance: Mechanisms of Sphingolipid Homeostasis. Molecular Cell 2010, 40: 267-279. PMID: 20965421, PMCID: PMC2987644, DOI: 10.1016/j.molcel.2010.10.005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSphingolipid homeostasisCell biologyEukaryotic cell biologyKey cellular rolesComplex membrane compositionCellular rolesSecretory pathwaySphingolipid biosynthesisEnzymatic machineryPhysiologic cuesSphingolipid metabolismMembrane compositionSphingolipidsBiologyNew insightsHomeostasisStructural componentsMembraneCellsBiosynthesisDefining featureMachineryGlycerolipidsEnzymeImproved understanding