2024
Scaleable production of highly loaded protein nanoparticles for immune modulation
Caplan M, Baldwin R, Yin X, Grishin A, Eisenbarth S, Sampson H, Bottomly K, Prud’homme R. Scaleable production of highly loaded protein nanoparticles for immune modulation. Communications Materials 2024, 5: 191. DOI: 10.1038/s43246-024-00626-w.Peer-Reviewed Original ResearchAdjuvants to antigen-presenting cellsImmune modulationAntigen-presenting cellsMurine immune systemImmune system cellsPeanut-allergic patientsDesensitizer applicationPLG nanoparticlesAntigen deliverySystemic exposurePoly(lactide-co-glycolideBasophil activationClinical investigationAllergic responsesImmune systemSystem cellsProtein antigensClinical applicationDelivery of proteinsE. coli phospholipidsSafety evidenceAntigenProtein nanoparticlesDeliveryCellsEditorial: Molecular mechanisms underlying polycystic kidney disease: from the smallest bricks to the big scenario
Di Mise A, Caplan M, Valenti G. Editorial: Molecular mechanisms underlying polycystic kidney disease: from the smallest bricks to the big scenario. Frontiers In Molecular Biosciences 2024, 11: 1429206. PMID: 38836108, PMCID: PMC11149700, DOI: 10.3389/fmolb.2024.1429206.Peer-Reviewed Original ResearchCalcium signalling and transport in the kidney
Staruschenko A, Alexander R, Caplan M, Ilatovskaya D. Calcium signalling and transport in the kidney. Nature Reviews Nephrology 2024, 20: 541-555. PMID: 38641658, DOI: 10.1038/s41581-024-00835-z.Peer-Reviewed Original ResearchCalcium channelsCalcium levelsCalcium-binding proteinSerum calcium levelsOptimal bone mineralizationPolycystic kidney diseaseIntracellular signaling mechanismsIntracellular second messengersRegulate calcium levelsCalcium handlingSevere complicationsFiltered calciumKidney diseaseCalcium transportRenal cellsCalcium homeostasisCalcium signalingFormation of kidney stonesCalcium dysregulationPhysiological stimuliKidney stonesBone mineralizationKidneySecond messengersSignaling mechanisms
2023
The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion
Onuchic L, Padovano V, Schena G, Rajendran V, Dong K, Shi X, Pandya R, Rai V, Gresko N, Ahmed O, Lam T, Wang W, Shen H, Somlo S, Caplan M. The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion. Nature Communications 2023, 14: 1790. PMID: 36997516, PMCID: PMC10063565, DOI: 10.1038/s41467-023-37449-1.Peer-Reviewed Original ResearchConceptsPolycystin-1Nicotinamide nucleotide transhydrogenaseTerminal tailCystic phenotypeAutosomal dominant polycystic kidney diseaseCyst cell proliferationC-terminal domainAmino acid residuesLethal monogenic disorderC-terminal cleavageNucleotide transhydrogenaseAcid residuesMitochondrial functionTransgenic expressionPKD1 geneRedox stateShort fragmentsCell proliferationMonogenic disordersDominant polycystic kidney diseasePolycystic kidney diseaseGene therapy strategiesProteinPhenotypeFragments
2022
Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR
Sempou E, Kostiuk V, Zhu J, Cecilia Guerra M, Tyan L, Hwang W, Camacho-Aguilar E, Caplan M, Zenisek D, Warmflash A, Owens N, Khokha M. Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR. Nature Communications 2022, 13: 6681. PMID: 36335122, PMCID: PMC9637099, DOI: 10.1038/s41467-022-34363-w.Peer-Reviewed Original ResearchConceptsPluripotent cellsAdult tissue homeostasisCell fate commitmentDifferentiated cell fatesLeft-right patterningPluripotent embryonic cellsHuman embryonic stem cellsTemporal transcriptome analysisGene regulatory networksExpense of differentiationEmbryonic stem cellsGerm layer differentiationMembrane depolarizationFate commitmentPluripotent stateCell fateTranscriptome analysisRegulatory networksMyogenic lineageEmbryonic developmentTissue homeostasisDifferentiated fateEmbryonic cellsCandidate genesPluripotencyPolycystin-2 in the Endoplasmic Reticulum: Bending Ideas about the Role of the Cilium
Caplan MJ. Polycystin-2 in the Endoplasmic Reticulum: Bending Ideas about the Role of the Cilium. Journal Of The American Society Of Nephrology 2022, 33: 1433-1434. PMID: 35906088, PMCID: PMC9342637, DOI: 10.1681/asn.2022050557.Peer-Reviewed Original ResearchAMPK and Polycystic Kidney Disease Drug Development: An Interesting Off-Target Target
Caplan MJ. AMPK and Polycystic Kidney Disease Drug Development: An Interesting Off-Target Target. Frontiers In Medicine 2022, 9: 753418. PMID: 35174190, PMCID: PMC8841847, DOI: 10.3389/fmed.2022.753418.Peer-Reviewed Original ResearchCellular signaling pathwaysPolycystic kidney diseasePolycystic kidney disease mutationCellular energy useProtein kinaseMaster regulatorCellular metabolismSignaling pathwaysDisease mutationsGenetic diseasesTissue architectureEnzyme activityDramatic perturbationsAutosomal dominant polycystic kidney diseasePathwayDominant polycystic kidney diseaseNew therapeuticsMutationsRenal tissue architectureDrug developmentCellsKinaseAMPKGeneration pathwaysGenes
2021
β3 adrenergic receptor as potential therapeutic target in ADPKD
Schena G, Carmosino M, Chiurlia S, Onuchic L, Mastropasqua M, Maiorano E, Schena FP, Caplan MJ. β3 adrenergic receptor as potential therapeutic target in ADPKD. Physiological Reports 2021, 9: e15058. PMID: 34676684, PMCID: PMC8531837, DOI: 10.14814/phy2.15058.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseΒ3-ARΒ3-adrenergic receptorTherapeutic targetKidney/body weight ratioΒ3-AR levelSympathetic nerve activityBody weight ratioType 2 receptorCyst-lining epithelial cellsDominant polycystic kidney diseaseRenal tubular cellsNovel therapeutic targetCyclic AMP accumulationPotential therapeutic targetVasopressin type 2 receptorHuman renal tissuePolycystic kidney diseaseFluid-filled cystsADPKD mouse modelNerve activityKidney functionKidney diseaseRenal parenchymaHealthy controls
2020
Chloride channels regulate differentiation and barrier functions of the mammalian airway
He M, Wu B, Ye W, Le DD, Sinclair AW, Padovano V, Chen Y, Li KX, Sit R, Tan M, Caplan MJ, Neff N, Jan YN, Darmanis S, Jan LY. Chloride channels regulate differentiation and barrier functions of the mammalian airway. ELife 2020, 9: e53085. PMID: 32286221, PMCID: PMC7182432, DOI: 10.7554/elife.53085.Peer-Reviewed Original ResearchConceptsChloride channelsSingle-cell RNA sequencingNon-redundant roleCellular programsCellular landscapeRNA sequencingMolecular eventsEpithelial progenitorsGenetic inactivationMucosal barrierAirway barrier functionDevelopmental landscapeBarrier functionAbnormal mucociliary clearanceMammalian airwaysProtective mucosal barrierAirway mucosal barrierHuman fetal developmentPrimary targetAirway formationAirway disordersAirway diseaseAirway defectsMucus obstructionMouse airwaysA cut above (and below): Protein cleavage in the regulation of polycystin trafficking and signaling
Padovano V, Mistry K, Merrick D, Gresko N, Caplan MJ. A cut above (and below): Protein cleavage in the regulation of polycystin trafficking and signaling. Cellular Signalling 2020, 72: 109634. PMID: 32283256, PMCID: PMC7269866, DOI: 10.1016/j.cellsig.2020.109634.Peer-Reviewed Original ResearchConceptsPolycystin-1Polycystin proteinsG proteinsPolycystin-1 proteinProtein maturationTerminal tailObligate stepBiological pathwaysProtein cleavagePhysiological functionsProteolytic siteProteinPathological consequencesAutosomal dominant polycystic kidney diseaseTraffickingDominant polycystic kidney diseasePolycystic kidney diseasePrimary functionCleavageRegulationMaturationGenesMitochondriaValuable insightsPathwayMechanisms involved in AMPK-mediated deposition of tight junction components to the plasma membrane
Wu J, Rowart P, Jouret F, Gassaway BM, Rajendran V, Rinehart J, Caplan MJ. Mechanisms involved in AMPK-mediated deposition of tight junction components to the plasma membrane. American Journal Of Physiology - Cell Physiology 2020, 318: c486-c501. PMID: 31913699, PMCID: PMC7099514, DOI: 10.1152/ajpcell.00422.2019.Peer-Reviewed Original ResearchConceptsJunction assemblyPlasma membranePhospho-defective mutantsEpithelial junction assemblyMDCK renal epithelial cellsProtein kinase activationJunction-associated proteinsRenal epithelial cellsActive GTPEpithelial polarizationTight junction componentsZO-1 localizationAMPK activationKinase activationKey regulatorAfadinAMPKImportant regulatorJunction componentsProtein zonula occludens-1Par3Epithelial cellsTight junction protein zonula occludens-1RegulatorAssembly
2019
Holding open the door reveals a new view of polycystin channel function
Caplan MJ. Holding open the door reveals a new view of polycystin channel function. EMBO Reports 2019, 20: embr201949156. PMID: 31556469, PMCID: PMC6832007, DOI: 10.15252/embr.201949156.Peer-Reviewed Original ResearchEverything You Always Wanted to Know about β3-AR * (* But Were Afraid to Ask)
Schena G, Caplan MJ. Everything You Always Wanted to Know about β3-AR * (* But Were Afraid to Ask). Cells 2019, 8: 357. PMID: 30995798, PMCID: PMC6523418, DOI: 10.3390/cells8040357.Peer-Reviewed Original ResearchConceptsNovel pharmacological approachesCurrent clinical practiceNovel therapeutic targetAR signalingΒ3-ARPharmacological approachesOcular diseasesTherapeutic targetAdrenergic receptorsClinical practiceFindings translateClinical areasCellular modelSuitable animalAppealing targetInter-species differencesDiseaseReceptors
2018
The Polycystin Complex Reveals Its Complexity
Padovano V, Caplan MJ. The Polycystin Complex Reveals Its Complexity. Biochemistry 2018, 57: 6917-6918. PMID: 30540438, DOI: 10.1021/acs.biochem.8b01205.Peer-Reviewed Original ResearchNewly synthesized polycystin‐1 takes different trafficking pathways to the apical and ciliary membranes
Gilder AL, Chapin HC, Padovano V, Hueschen CL, Rajendran V, Caplan MJ. Newly synthesized polycystin‐1 takes different trafficking pathways to the apical and ciliary membranes. Traffic 2018, 19: 933-945. PMID: 30125442, PMCID: PMC6237641, DOI: 10.1111/tra.12612.Peer-Reviewed Original ResearchConceptsPolycystin-1Ciliary deliveryBrefeldin AApical deliveryRenal epithelial cellsN-terminal fragmentPolycystin-2LLC-PK1 renal epithelial cellsDifferent trafficking pathwaysTrans-Golgi networkApical membraneEpithelial cellsCultured epithelial cellsTrafficking pathwaysTransmembrane proteinGolgi compartmentPrimary ciliaC-terminal fragmentCiliary membraneC-terminusAutocatalytic cleavageDistinct pathwaysIncubating cellsCell membraneAutosomal dominant polycystic kidney diseasePolycystin-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 diseaseMetabolism and mitochondria in polycystic kidney disease research and therapy
Padovano V, Podrini C, Boletta A, Caplan MJ. Metabolism and mitochondria in polycystic kidney disease research and therapy. Nature Reviews Nephrology 2018, 14: 678-687. PMID: 30120380, DOI: 10.1038/s41581-018-0051-1.Peer-Reviewed Original ResearchConceptsPolycystic kidney disease 1Polycystin-1Autosomal dominant polycystic kidney diseaseHallmark of ADPKDFluid-filled renal cystsPolycystin proteinsADPKD cellsPKD genesMolecular mechanismsOxidative phosphorylationCell metabolismRegulatory rolePhysiological functionsADPKD pathogenesisEnergy metabolismPotential therapeutic targetMonogenic diseasesEnergy productionMitochondriaDominant polycystic kidney diseasePolycystic kidney diseaseTherapeutic targetMutationsAlternative pathwayMetabolismImplications of AMPK in the Formation of Epithelial Tight Junctions
Rowart P, Wu J, Caplan MJ, Jouret F. Implications of AMPK in the Formation of Epithelial Tight Junctions. International Journal Of Molecular Sciences 2018, 19: 2040. PMID: 30011834, PMCID: PMC6073107, DOI: 10.3390/ijms19072040.Peer-Reviewed Original ResearchConceptsTJ assemblyPlasma membraneAMPK activationUbiquitous serine/threonine kinaseSerine/threonine kinaseBaso-lateral domainTight junctionsImplication of AMPKSelective paracellular permeabilityCell polarityThreonine kinaseDisruption of TJsProtein kinaseEnergy sensorTJ regulationΓ subunitMembrane componentsZO-1 distributionAssembly/AMPKEpithelial tight junctionsEssential roleZonula occludensKinaseEpithelial cellsAdvances & challenges in developing gene therapies for rare kidney diseases
Padovano V, Caplan M. Advances & challenges in developing gene therapies for rare kidney diseases. Cell And Gene Therapy Insights 2018, 4: 951-964. DOI: 10.18609/cgti.2018.094.Peer-Reviewed Original Research
2017
The secretory pathway at 50: a golden anniversary for some momentous grains of silver
Matlin KS, Caplan MJ. The secretory pathway at 50: a golden anniversary for some momentous grains of silver. Molecular Biology Of The Cell 2017, 28: 229-232. PMID: 28082520, PMCID: PMC5231891, DOI: 10.1091/mbc.e16-07-0508.Peer-Reviewed Original ResearchConceptsSecretory pathwayBiosynthetic machineryMembrane protein trafficSpecialized cell typesCell's biosynthetic machineryModern cell biologyProtein trafficCell biologyCell typesMorphological methodologiesPathological consequencesPathwayMachineryCentral paradigmBiologyDynamic natureSecretoryCulmination of decadesCellsAdaptationDiscovery