2020
Mechanisms 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
2016
Newly synthesized and recycling pools of the apical protein gp135 do not occupy the same compartments
Stoops EH, Hull M, Caplan MJ. Newly synthesized and recycling pools of the apical protein gp135 do not occupy the same compartments. Traffic 2016, 17: 1272-1285. PMID: 27649479, PMCID: PMC5123909, DOI: 10.1111/tra.12449.Peer-Reviewed Original ResearchConceptsApical early endosomesPlasma membrane proteinsPolarized epithelial cellsApical recycling endosomesDistinct trafficking pathwaysSNAP-tag systemBasolateral membrane domainsProtein sortingApical proteinsRecycling endosomesTrafficking pathwaysGolgi networkProtein trafficMembrane domainsMembrane proteinsEarly endosomesPlasma membraneInitial traffickingEndosomesApical membraneProteinGp135Same compartmentEpithelial cellsTrafficking
2015
The periciliary ring in polarized epithelial cells is a hot spot for delivery of the apical protein gp135
Stoops EH, Hull M, Olesen C, Mistry K, Harder JL, Rivera-Molina F, Toomre D, Caplan MJ. The periciliary ring in polarized epithelial cells is a hot spot for delivery of the apical protein gp135. Journal Of Cell Biology 2015, 211: 287-294. PMID: 26504168, PMCID: PMC4621837, DOI: 10.1083/jcb.201502045.Peer-Reviewed Original ResearchConceptsPrimary ciliaSurface proteinsTrans-Golgi networkPolarized epithelial cellsApical surface proteinsSNAP-tag systemBasolateral plasma membraneCell surface proteinsEpithelial cellsApical proteinsPericiliary regionGolgi networkPolarized traffickingCarrier vesiclesProtein deliveryPlasma membraneApical membraneProteinGp135Basolateral membraneCiliaMembraneHot spotsCellsTraffickingDual pulse-chase microscopy reveals early divergence in the biosynthetic trafficking of the Na,K-ATPase and E-cadherin
Farr GA, Hull M, Stoops EH, Bateson R, Caplan MJ. Dual pulse-chase microscopy reveals early divergence in the biosynthetic trafficking of the Na,K-ATPase and E-cadherin. Molecular Biology Of The Cell 2015, 26: 4401-4411. PMID: 26424804, PMCID: PMC4666135, DOI: 10.1091/mbc.e14-09-1385.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkPlasma membraneE-cadherinK-ATPasePolarized MDCK epithelial cellsPost-Golgi traffickingCell surfacePolarized epithelial cellsEpithelial cellsMDCK epithelial cellsDistinct trafficking routesBiosynthetic traffickingCarrier vesiclesSecretory pathwayMembrane proteinsSurface deliveryBasolateral domainMost proteinsTrafficking routesGolgi complexTemperature blockTraffickingProteinMembraneCellsAkt Substrate of 160 kD Regulates Na+,K+-ATPase Trafficking in Response to Energy Depletion and Renal Ischemia
Alves DS, Thulin G, Loffing J, Kashgarian M, Caplan MJ. Akt Substrate of 160 kD Regulates Na+,K+-ATPase Trafficking in Response to Energy Depletion and Renal Ischemia. Journal Of The American Society Of Nephrology 2015, 26: 2765-2776. PMID: 25788531, PMCID: PMC4625659, DOI: 10.1681/asn.2013101040.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiotinylationCell LineCytoplasmDogsDynaminsEndocytosisEpithelial CellsGTPase-Activating ProteinsHumansIschemiaKidneyKidney DiseasesMadin Darby Canine Kidney CellsMaleMiceMice, KnockoutMicroscopy, FluorescencePhosphorylationProtein TransportReperfusion InjuryRNA, Small InterferingSignal TransductionSodium-Potassium-Exchanging ATPaseConceptsRenal epithelial cellsATPase traffickingIntracellular compartmentsEpithelial cell polarityEpithelial cellsBasolateral plasma membraneGlucose transporter 4Cultured epithelial cellsCell polarityRab GTPaseAkt substratePlasma membraneSubcellular distributionAS160Energy depletionDirect bindingTransporter 4TraffickingDirect roleK-ATPaseATPaseTubular soluteIntracellular accumulationCellsCompartments
2013
Epithelial morphogenesis of MDCK cells in three-dimensional collagen culture is modulated by interleukin-8
Wells EK, Yarborough O, Lifton RP, Cantley LG, Caplan MJ. Epithelial morphogenesis of MDCK cells in three-dimensional collagen culture is modulated by interleukin-8. American Journal Of Physiology - Cell Physiology 2013, 304: c966-c975. PMID: 23485708, PMCID: PMC3651639, DOI: 10.1152/ajpcell.00261.2012.Peer-Reviewed Original ResearchConceptsMDCK cellsEpithelial morphogenesisHepatocyte growth factorGene expressionMDCK culturesDifferential gene expressionThree-dimensional collagen culturesReal-time PCR analysisGreater expression differencesMDCK cystsRenal epithelial cellsCollagen gelsGene setsTwo-dimensional cultureExpression differencesHGF stimulationThree-dimensional cultureMicroarray analysisSpherical cystsIL-8 protein expressionPCR analysisTubule-like structuresIL-8 participatesCollagen culturesProtein levelsActivation of the Ca2+-sensing receptor induces deposition of tight junction components to the epithelial cell plasma membrane
Jouret F, Wu J, Hull M, Rajendran V, Mayr B, Schöfl C, Geibel J, Caplan MJ. Activation of the Ca2+-sensing receptor induces deposition of tight junction components to the epithelial cell plasma membrane. Journal Of Cell Science 2013, 126: 5132-5142. PMID: 24013548, PMCID: PMC3828589, DOI: 10.1242/jcs.127555.Peer-Reviewed Original ResearchConceptsTJ assemblyMDCK cellsStable transfectionFunction mutant formZO-1Tight junction components ZO-1G protein-coupled receptorsHuman CaSRCell-cell contactEpithelial cell plasma membranesMadin-Darby canine kidney cellsCell plasma membraneStimulation of CaSRDivalent ion homeostasisCanine kidney cellsTight junctionsJunction-associated proteinsTight junction componentsEndogenous CaSRProtein kinasePlasma membraneIon homeostasisMutant formsChelator BAPTA-AMCell differentiation
2012
VIP17/MAL expression modulates epithelial cyst formation and ciliogenesis
Takiar V, Mistry K, Carmosino M, Schaeren-Wiemers N, Caplan MJ. VIP17/MAL expression modulates epithelial cyst formation and ciliogenesis. American Journal Of Physiology - Cell Physiology 2012, 303: c862-c871. PMID: 22895261, PMCID: PMC3469709, DOI: 10.1152/ajpcell.00338.2011.Peer-Reviewed Original ResearchConceptsRenal cystogenesisPrimary ciliaVectorial solute transportApical vesicle transportConsequence of defectsEpithelial cellsEpithelial cyst formationPolarized organizationRenal epithelial cellsBasolateral markersVesicle transportIntegral proteinsAbsent ciliaCiliary defectsExpression resultsAberrant sortingCiliary morphologyOverexpressing cellsImmunofluorescence analysisCiliaCystogenesisCiliogenesisOverexpressionCyst developmentTransgenic mice
2011
Preactivation of AMPK by metformin may ameliorate the epithelial cell damage caused by renal ischemia
Seo-Mayer PW, Thulin G, Zhang L, Alves DS, Ardito T, Kashgarian M, Caplan MJ. Preactivation of AMPK by metformin may ameliorate the epithelial cell damage caused by renal ischemia. American Journal Of Physiology. Renal Physiology 2011, 301: f1346-f1357. PMID: 21849490, PMCID: PMC3233870, DOI: 10.1152/ajprenal.00420.2010.Peer-Reviewed Original ResearchConceptsEpithelial cell polarityMDCK cellsPlasma membrane domainsIon transport proteinsEpithelial cell organizationCellular energy sensorAMPK activator metforminMadin-Darby canine kidney cellsBasolateral plasma membraneShort hairpin RNACanine kidney cellsCell polarityImmunofluoresence localizationRenal epithelial cellsMembrane domainsNa-K-ATPaseProtein kinaseAMPK activatorPlasma membraneVesicular compartmentsAMPK activityTransport proteinsEnergy sensorMolecular consequencesBasolateral localizationAMP-activated Protein Kinase (AMPK) Activation and Glycogen Synthase Kinase-3β (GSK-3β) Inhibition Induce Ca2+-independent Deposition of Tight Junction Components at the Plasma Membrane* ♦
Zhang L, Jouret F, Rinehart J, Sfakianos J, Mellman I, Lifton RP, Young LH, Caplan MJ. AMP-activated Protein Kinase (AMPK) Activation and Glycogen Synthase Kinase-3β (GSK-3β) Inhibition Induce Ca2+-independent Deposition of Tight Junction Components at the Plasma Membrane* ♦. Journal Of Biological Chemistry 2011, 286: 16879-16890. PMID: 21383016, PMCID: PMC3089531, DOI: 10.1074/jbc.m110.186932.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsCadherinsCalciumCell AdhesionCell MembraneDogsEpitheliumGene Expression Regulation, EnzymologicGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaMembrane ProteinsMicroscopy, FluorescencePhosphoproteinsPhosphorylationRNA InterferenceTight JunctionsZonula Occludens-1 ProteinConceptsProtein kinase activationTight junction componentsJunction componentsPlasma membraneAMPK activationKinase activationGSK-3β inhibitionNectin-afadin systemEpithelial tight junctionsTight junctionsPhosphorylation studiesSynthase kinaseJunctional proteinsAbsence of extracellularDistinct pathwaysCell growthE-cadherinIndependent depositionKinaseActivationInduce Ca2MembraneAfadinExtracellularInhibitionActivating AMP-activated protein kinase (AMPK) slows renal cystogenesis
Takiar V, Nishio S, Seo-Mayer P, King JD, Li H, Zhang L, Karihaloo A, Hallows KR, Somlo S, Caplan MJ. Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 2462-2467. PMID: 21262823, PMCID: PMC3038735, DOI: 10.1073/pnas.1011498108.Peer-Reviewed Original ResearchConceptsCystic fibrosis transmembrane conductance regulatorRenal cystogenesisProtein kinaseAutosomal dominant polycystic kidney diseaseFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorEpithelial cellsCyst epithelial cellsRenal cyst developmentCyst-lining epithelial cellsAMPK activationConductance regulatorRapamycin (mTOR) pathwayMammalian targetPharmacological activatorsChloride channelsMTOR pathwayCystogenesisCyst developmentKinaseAMPKContext of ADPKDSignificant arrestDominant polycystic kidney diseasePolycystic kidney disease
2010
AS160 Associates with the Na+,K+-ATPase and Mediates the Adenosine Monophosphate-stimulated Protein Kinase-dependent Regulation of Sodium Pump Surface Expression
Alves DS, Farr GA, Seo-Mayer P, Caplan MJ. AS160 Associates with the Na+,K+-ATPase and Mediates the Adenosine Monophosphate-stimulated Protein Kinase-dependent Regulation of Sodium Pump Surface Expression. Molecular Biology Of The Cell 2010, 21: 4400-4408. PMID: 20943949, PMCID: PMC3002392, DOI: 10.1091/mbc.e10-06-0507.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsBiological TransportCell LineChlorocebus aethiopsCOS CellsDogsDose-Response Relationship, DrugEndocytosisEpithelial CellsGene ExpressionGene Knockdown TechniquesGTPase-Activating ProteinsHumansImmunoprecipitationPhosphorylationPyrazolesPyrimidinesSignal TransductionSodium-Potassium-Exchanging ATPaseConceptsRab-GTPase-activating proteinMost epithelial cell typesCompound CProtein kinase‐dependent regulationKinase-dependent regulationActive transport proteinsMadin-Darby canine kidneyEpithelial cell typesRegulated endocytosisShort hairpin RNASurface expressionATPase endocytosisCell surface expressionProtein kinasePlasma membraneCOS cellsTransport proteinsΑ-subunitHairpin RNAAS160Cell typesIntracellular retentionVariety of mechanismsATPaseATPase activityAssociation with β-COP Regulates the Trafficking of the Newly Synthesized Na,K-ATPase*
Morton MJ, Farr GA, Hull M, Capendeguy O, Horisberger JD, Caplan MJ. Association with β-COP Regulates the Trafficking of the Newly Synthesized Na,K-ATPase*. Journal Of Biological Chemistry 2010, 285: 33737-33746. PMID: 20801885, PMCID: PMC2962472, DOI: 10.1074/jbc.m110.141119.Peer-Reviewed Original ResearchConceptsK-ATPase αK-ATPase β-subunitΒ-COPΒ-subunitΑ-subunitPlasma membraneEndoplasmic reticulumK-ATPase α-subunitMutant α-subunitsIon-transporting ATPasePlasma membrane expressionK-ATPasePulse-chase experimentsPartner proteinsNovel labeling techniqueCoat proteinDibasic motifCell surfaceMembrane expressionObligate intermediateΒ subunit expressionProteinReticulumLymphocytes Accelerate Epithelial Tight Junction Assembly: Role of AMP-Activated Protein Kinase (AMPK)
Tang XX, Chen H, Yu S, Zhang L, Caplan MJ, Chan HC. Lymphocytes Accelerate Epithelial Tight Junction Assembly: Role of AMP-Activated Protein Kinase (AMPK). PLOS ONE 2010, 5: e12343. PMID: 20808811, PMCID: PMC2925955, DOI: 10.1371/journal.pone.0012343.Peer-Reviewed Original ResearchConceptsTJ assemblyActivation of AMPKProtein kinaseEpithelial cellsCalcium switch experimentsEpithelial cell polaritySuppression of AMPKTight junction assemblyRole of AMPMadin-Darby canine kidney cellsCellular ATP levelsCanine kidney cellsTight junctionsCell polarityApicolateral borderJunction assemblyModel cell lineAMPK activationProper formationAdjacent epithelial cellsTJ formationChemical inhibitorsCalu-3 human airway epithelial cellsHuman airway epithelial cellsMDCK cells
2009
Membrane proteins follow multiple pathways to the basolateral cell surface in polarized epithelial cells
Farr GA, Hull M, Mellman I, Caplan MJ. Membrane proteins follow multiple pathways to the basolateral cell surface in polarized epithelial cells. Journal Of Cell Biology 2009, 186: 269-282. PMID: 19620635, PMCID: PMC2717640, DOI: 10.1083/jcb.200901021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportCadherinsCell LineCell MembraneCell PolarityDogsEndosomesEpithelial CellsExocytosisGolgi ApparatusHumansMembrane GlycoproteinsMembrane ProteinsModels, MolecularProtein Structure, SecondaryProtein TransportReceptors, TransferrinRecombinant Fusion ProteinsSodium-Potassium-Exchanging ATPaseStaining and LabelingTrans-Golgi NetworkViral Envelope ProteinsConceptsBasolateral proteinsMembrane proteinsSurface deliveryK-ATPaseVesicular stomatitis virus G proteinPolarized epithelial cellsBasolateral membrane proteinsEpithelial cellsVirus G proteinBasolateral cell surfaceBasolateral deliveryTransport intermediatesGolgi networkSmall GTPasesPlasma membraneG proteinsCell surfaceProteinMultiple pathwaysBasolateral membraneGolgiPathwayCellsMembraneGTPases
2008
Exon Loss Accounts for Differential Sorting of Na-K-Cl Cotransporters in Polarized Epithelial Cells
Carmosino M, Giménez I, Caplan M, Forbush B. Exon Loss Accounts for Differential Sorting of Na-K-Cl Cotransporters in Polarized Epithelial Cells. Molecular Biology Of The Cell 2008, 19: 4341-4351. PMID: 18667527, PMCID: PMC2555935, DOI: 10.1091/mbc.e08-05-0478.Peer-Reviewed Original ResearchConceptsDileucine motifNa-K-Cl cotransporterRenal Na-K-Cl cotransporterPolarized epithelial cellsAmino acid stretchApical proteinsApical sortingEvolutionary lossRenal epithelial cell lineGene structurePhylogenetic analysisDifferential sortingDirect traffickingEpithelial cell lineAdditional exonC-terminusMammalian kidneyApical membraneExonsNovel mechanismNKCC2 geneCell linesBasolateral membraneMotifEpithelial cells
2006
AMP-activated protein kinase regulates the assembly of epithelial tight junctions
Zhang L, Li J, Young LH, Caplan MJ. AMP-activated protein kinase regulates the assembly of epithelial tight junctions. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 17272-17277. PMID: 17088526, PMCID: PMC1859922, DOI: 10.1073/pnas.0608531103.Peer-Reviewed Original ResearchConceptsTight junction assemblyJunction assemblyProtein kinaseLKB1-dependent phosphorylationCell polarization processCellular energy statusActivation of AMPKTight junctionsEukaryotic cellsTight junction structureAMPKMDCK cellsEpithelial tight junctionsEnergy statusKinaseEpithelial cellsAbsence of Ca2AssemblyTransepithelial electrical resistanceParacellular fluxZonula occludens-1CellsRecent studiesOccludens-1LKB1
2005
The C-Terminal Tail of the Polycystin-1 Protein Interacts with the Na,K-ATPase α-Subunit
Zatti A, Chauvet V, Rajendran V, Kimura T, Pagel P, Caplan MJ. The C-Terminal Tail of the Polycystin-1 Protein Interacts with the Na,K-ATPase α-Subunit. Molecular Biology Of The Cell 2005, 16: 5087-5093. PMID: 16107561, PMCID: PMC1266409, DOI: 10.1091/mbc.e05-03-0200.Peer-Reviewed Original ResearchConceptsC-terminal tailPolycystin-1Cytoplasmic C-terminal tailK-ATPase α-subunitPolycystin-1 proteinK-ATPase activityRegulation of NaChinese hamster ovary cellsProtein interactsHamster ovary cellsProtein exhibitΑ-subunitFunctional studiesAmino acidsPKD1 geneOvary cellsAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseasePolycystic kidney diseaseInteractsKinetic propertiesRegulationGenesTailProtein
2004
Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus
Chauvet V, Tian X, Husson H, Grimm DH, Wang T, Hieseberger T, Igarashi P, Bennett AM, Ibraghimov-Beskrovnaya O, Somlo S, Caplan MJ. Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. Journal Of Clinical Investigation 2004, 114: 1433-1443. PMID: 15545994, PMCID: PMC525739, DOI: 10.1172/jci21753.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell LineCell NucleusChlorocebus aethiopsCHO CellsCOS CellsCricetinaeCricetulusDogsEmbryo, MammalianEpithelial CellsKidney TubulesMembrane ProteinsMiceMice, TransgenicPolycystic Kidney, Autosomal DominantProteinsSequence DeletionSignal TransductionStress, MechanicalTranscription Factor AP-1TRPP Cation ChannelsConceptsC-terminal tailAutosomal dominant polycystic kidney diseaseCell-matrix interactionsCiliary signalingSecond genePolycystin-2Polycystin-1C-terminusNovel pathwayProteolytic cleavageNuclear translocationMechanical stimuliGenesDominant polycystic kidney diseasePolycystic kidney diseasePrecise mechanismCleavageTerminusSignalingTranslocationNucleusPathwaySorting of H,K‐ATPase β‐Subunit in MDCK and LLC‐PK1 Cells is Independent of μ1B Adaptin Expression
Duffield A, Fölsch H, Mellman I, Caplan MJ. Sorting of H,K‐ATPase β‐Subunit in MDCK and LLC‐PK1 Cells is Independent of μ1B Adaptin Expression. Traffic 2004, 5: 449-461. PMID: 15117319, DOI: 10.1111/j.1398-9219.2004.00192.x.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex mu SubunitsAdaptor Proteins, Vesicular TransportAmino Acid MotifsAnimalsCell LineCytoplasmDogsEpithelial CellsGlutathione TransferaseH(+)-K(+)-Exchanging ATPaseLLC-PK1 CellsMembrane ProteinsProtein SubunitsProtein TransportReceptors, LDLReceptors, TransferrinRecombinant Fusion ProteinsSwineTransfectionTyrosineConceptsLow-density lipoproteinTransferrin receptorBasolateral localizationTyrosine-based motifMDCK cellsB expressionLLC-PK1 cellsEpithelial cellsLipoproteinMadin-Darby canine kidney cellsCertain epithelial cellsReceptorsKidney cellsCanine kidney cellsK-ATPase beta subunitCellsDifferential expressionK-ATPaseBasolateral expressionExpressionApical membrane