2024
Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment
Sun F, Wang H, Wu J, Quraishi I, Zhang Y, Pedram M, Gao B, Jonas E, Nguyen V, Wu S, Mabrouk O, Jafar-nejad P, Kaczmarek L. Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment. Biomolecules 2024, 14: 1397. PMID: 39595574, PMCID: PMC11591899, DOI: 10.3390/biom14111397.Peer-Reviewed Original ResearchWild-type miceKO miceSpectrum of epilepsy syndromesAntisense oligonucleotidesGain-of-function variantsAntisense oligonucleotide treatmentEpileptic phenotypePotassium channelsKCNT1Molecular profilingOligonucleotide treatmentAnimal modelsEpilepsy syndromesC-terminal mutationsIncreased expressionCerebral cortexMiceExpression of multiple proteinsComprehensive proteomic analysisDisease modelsCortical mitochondriaMolecular differencesDensity of mitochondrial cristaeMitochondrial membraneTreatment
2021
Presynaptic Kv3 channels are required for fast and slow endocytosis of synaptic vesicles
Wu XS, Subramanian S, Zhang Y, Shi B, Xia J, Li T, Guo X, El-Hassar L, Szigeti-Buck K, Henao-Mejia J, Flavell RA, Horvath TL, Jonas EA, Kaczmarek LK, Wu LG. Presynaptic Kv3 channels are required for fast and slow endocytosis of synaptic vesicles. Neuron 2021, 109: 938-946.e5. PMID: 33508244, PMCID: PMC7979485, DOI: 10.1016/j.neuron.2021.01.006.Peer-Reviewed Original ResearchConceptsSlow endocytosisVesicle mobilizationF-actin cytoskeletonChannel mutationsPotassium channelsKv3.3 proteinsInhibits endocytosisRapid endocytosisNovel functionF-actinEndocytosisCrucial functionSynaptic vesiclesFamily channelsSynaptic transmissionDiscovery decadesMembrane potentialNeurotransmitter releaseDiverse neurological disordersIon conductanceMutationsReleasable poolMouse nerve terminalsPotassium channel mutationsPathological effects
2011
Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential
Chen YB, Aon MA, Hsu YT, Soane L, Teng X, McCaffery JM, Cheng WC, Qi B, Li H, Alavian KN, Dayhoff-Brannigan M, Zou S, Pineda FJ, O'Rourke B, Ko YH, Pedersen PL, Kaczmarek LK, Jonas EA, Hardwick JM. Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential. Journal Of Cell Biology 2011, 195: 263-276. PMID: 21987637, PMCID: PMC3198165, DOI: 10.1083/jcb.201108059.Peer-Reviewed Original ResearchConceptsMitochondrial membrane potentialMitochondrial membraneMitochondrial ATP synthase β-subunitATP synthase β subunitBcl-2 family proteinsOuter membrane permeabilizationInner mitochondrial membrane potentialMembrane potentialMitochondrial energetic capacityOuter mitochondrial membraneSynthase β subunitInner mitochondrial membraneInner membrane potentialATP synthaseFamily proteinsBiochemical approachesGenetic evidenceEndogenous BclMembrane permeabilizationCellular resourcesΒ-subunitBcl-xLMitochondrial energeticsEnergetic capacityMitochondrial cristae
2008
PKC-Induced Intracellular Trafficking of CaV2 Precedes Its Rapid Recruitment to the Plasma Membrane
Zhang Y, Helm JS, Senatore A, Spafford JD, Kaczmarek LK, Jonas EA. PKC-Induced Intracellular Trafficking of CaV2 Precedes Its Rapid Recruitment to the Plasma Membrane. Journal Of Neuroscience 2008, 28: 2601-2612. PMID: 18322103, PMCID: PMC2830008, DOI: 10.1523/jneurosci.4314-07.Peer-Reviewed Original ResearchConceptsProtein kinase CActivation of PKCPlasma membraneGrowth conesLatrunculin BIntracellular traffickingActin polymerizationIntact microtubulesIntact actinKinase CChannel insertionPKC activationIon channelsMicrotubule polymerizationRapid recruitmentOrganellesLamellipodiumSubunitsMicrotubulesActinMembraneActivationRecruitmentCone terminalsNew sites
2007
Bcl-xL Inhibitor ABT-737 Reveals a Dual Role for Bcl-xL in Synaptic Transmission
Hickman JA, Hardwick JM, Kaczmarek LK, Jonas EA. Bcl-xL Inhibitor ABT-737 Reveals a Dual Role for Bcl-xL in Synaptic Transmission. Journal Of Neurophysiology 2007, 99: 1515-1522. PMID: 18160428, PMCID: PMC2836590, DOI: 10.1152/jn.00598.2007.Peer-Reviewed Original ResearchConceptsMitochondrial outer membraneEndogenous Bcl-xLMitochondrial channel activityBcl-xLInhibitor ABT-737ABT-737Outer membraneBcl-xL.Pro-apoptotic cleavage productRecombinant Bcl-xLChannel activityBcl-xL proteinSynaptic functionDual roleGenetic toolsDomain pocketSynaptic transmissionSynaptic activityGiant presynaptic terminalEquivalent modificationEndogenous proteolysisRepetitive synaptic activityBH3Cleavage productsProtein
2006
Mitochondrial factors with dual roles in death and survival
Cheng WC, Berman SB, Ivanovska I, Jonas EA, Lee SJ, Chen Y, Kaczmarek LK, Pineda F, Hardwick JM. Mitochondrial factors with dual roles in death and survival. Oncogene 2006, 25: 4697-4705. PMID: 16892083, DOI: 10.1038/sj.onc.1209596.Peer-Reviewed Original ResearchConceptsBcl-2 family proteinsCell deathCell death regulatorsPro-death Bcl-2 family proteinNormal cellular functionMitochondrial fission proteinDeath regulatorsDeath stimuliCellular functionsFamily proteinsMitochondrial factorsFission proteinsCell survivalBiochemical mechanismsCaspasesDual roleProteinHealthy cellsCellsMammalsMitochondriaRegulatorSurvivalDeathStretch
2005
Actions of BAX on Mitochondrial Channel Activity and on Synaptic Transmission
Jonas EA, Hardwick JM, Kaczmarek LK. Actions of BAX on Mitochondrial Channel Activity and on Synaptic Transmission. Antioxidants & Redox Signaling 2005, 7: 1092-1100. PMID: 16115013, DOI: 10.1089/ars.2005.7.1092.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisbcl-2-Associated X Proteinbcl-X ProteinCell MembraneElectrophysiologyIntracellular MembranesLiposomesLoligoMitochondriaMultigene FamilyNeurotransmitter AgentsPatch-Clamp TechniquesPeptidesPresynaptic TerminalsProtein Structure, TertiarySynapsesSynaptic TransmissionTime FactorsConceptsMitochondrial membraneBcl-2 family proteins BaxCell deathOuter mitochondrial membraneAction of BaxMitochondrial channel activityChannel activityNormal physiological settingsAntiapoptotic Bcl-xL proteinBcl-xL proteinDeath channelMitochondrial architectureMitochondrial channelsProapoptotic fragmentsLarge conductance channelPresynaptic terminalsBcl-xL.Proapoptotic proteinsAlternative functionsProtein BaxPhysiological settingsPhysiological roleSynaptic transmissionBaxNeurotransmitter release
2004
Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse*
Jonas EA, Hickman JA, Hardwick JM, Kaczmarek LK. Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse*. Journal Of Biological Chemistry 2004, 280: 4491-4497. PMID: 15561723, DOI: 10.1074/jbc.m410661200.Peer-Reviewed Original ResearchConceptsMitochondrial channel activityMitochondrial membraneChannel activityBcl-xLBcl-2 family proteinsPro-apoptotic fragmentsOuter mitochondrial membraneTrigger cell deathZ-VAD-FMKBenzyloxycarbonyl-VADFamily proteinsSynaptic responsesMulticonductance channelLarge conductance channelFluoromethyl ketoneCell deathMinutes of hypoxiaResponses of neuronsNeuronal functionSquid giant synapseSynaptic mitochondriaEarly eventsSynaptic functionHypoxic conditionsNeuronal deathProapoptotic N-truncated BCL-xL protein activates endogenous mitochondrial channels in living synaptic terminals
Jonas EA, Hickman JA, Chachar M, Polster BM, Brandt TA, Fannjiang Y, Ivanovska I, Basañez G, Kinnally KW, Zimmerberg J, Hardwick JM, Kaczmarek LK. Proapoptotic N-truncated BCL-xL protein activates endogenous mitochondrial channels in living synaptic terminals. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 13590-13595. PMID: 15342906, PMCID: PMC518799, DOI: 10.1073/pnas.0401372101.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisbcl-X ProteinDecapodiformesElectric ConductivityEndopeptidasesHypoxiaIon ChannelsLiposomesMitochondriaNADPatch-Clamp TechniquesPorinsPresynaptic TerminalsProtein Processing, Post-TranslationalProto-Oncogene Proteins c-bcl-2Sequence DeletionVoltage-Dependent Anion ChannelsConceptsBcl-xLMitochondrial channelsDeath pathwaysMitochondrial membraneBcl-xL.Proapoptotic Bcl-2 family proteinsVoltage-dependent anion channelBcl-2 family proteinsOuter mitochondrial membraneCell death pathwaysHydrophobic C-terminusBcl-xL proteinAntiapoptotic Bcl-xLNeuronal death pathwaysDeath stimuliBH3 domainFamily proteinsSquid presynaptic terminalsMammalian cellsC-terminusAnion channelMitochondriaChannel activityOpposite effectHealthy neuronsIon channels on intracellular organelles
Kaczmarek L, Jonas E. Ion channels on intracellular organelles. Advances In Molecular And Cell Biology 2004, 32: 433-458. DOI: 10.1016/s1569-2558(03)32018-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsExternal signalsIon channelsCellular functionsInner membraneMitochondrial channelsIntracellular membranesPlasma membraneIntracellular organellesMolecular identityCell deathCytoplasmic calcium levelsHandling of calciumRyanodine receptorProperties of channelsCytoplasmic calciumIntracellular storesPotential roleRelease of calciumInternal storesMembraneRegulationKey roleSynaptic transmissionCalcium influxIntracellular calcium
2003
Modulation of Synaptic Transmission by the BCL-2 Family Protein BCL-xL
Jonas EA, Hoit D, Hickman JA, Brandt TA, Polster BM, Fannjiang Y, McCarthy E, Montanez MK, Hardwick JM, Kaczmarek LK. Modulation of Synaptic Transmission by the BCL-2 Family Protein BCL-xL. Journal Of Neuroscience 2003, 23: 8423-8431. PMID: 12968005, PMCID: PMC6740692, DOI: 10.1523/jneurosci.23-23-08423.2003.Peer-Reviewed Original ResearchConceptsBcl-2 family proteinsProtein Bcl-xLBcl-xLFamily proteinsMitochondrial membranePro-apoptotic cleavage productRecombinant Bcl-xLBcl-xL proteinMitochondrial calcium uptakePresynaptic terminalsInfluences synaptic transmissionCell deathGiant presynaptic terminalSynaptic transmissionChannel activityProteinSquid stellate ganglionMitochondriaCleavage productsSynaptic stabilityAdult brainPostsynaptic responsesCalcium uptakeMembranePatch pipetteModulation of mitochondrial function by endogenous Zn2+ pools
Sensi SL, Ton-That D, Sullivan PG, Jonas EA, Gee KR, Kaczmarek LK, Weiss JH. Modulation of mitochondrial function by endogenous Zn2+ pools. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 6157-6162. PMID: 12724524, PMCID: PMC156342, DOI: 10.1073/pnas.1031598100.Peer-Reviewed Original ResearchConceptsDirect patch-clamp recordingsCultured cortical neuronsPatch-clamp recordingsCertain brain regionsNeuronal injuryPool of intracellularCortical neuronsIntact neuronsReactive oxygen species generationPostsynaptic neuronsClamp recordingsSynaptic spacePotent effectsBrain regionsOxygen species generationBrain mitochondriaMitochondrial poolMembrane depolarizationNeuronsRecent evidenceFurther studiesMitochondrial functionROS generationNovel evidenceSpecies generationBAK Alters Neuronal Excitability and Can Switch from Anti- to Pro-Death Function during Postnatal Development
Fannjiang Y, Kim CH, Huganir RL, Zou S, Lindsten T, Thompson CB, Mito T, Traystman RJ, Larsen T, Griffin DE, Mandir AS, Dawson TM, Dike S, Sappington AL, Kerr DA, Jonas EA, Kaczmarek LK, Hardwick JM. BAK Alters Neuronal Excitability and Can Switch from Anti- to Pro-Death Function during Postnatal Development. Developmental Cell 2003, 4: 575-585. PMID: 12689595, DOI: 10.1016/s1534-5807(03)00091-1.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnimals, NewbornApoptosisbcl-2 Homologous Antagonist-Killer ProteinCentral Nervous SystemCentral Nervous System DiseasesCentral Nervous System Viral DiseasesDisease Models, AnimalEpilepsyExcitatory Postsynaptic PotentialsGenetic VectorsHippocampusKainic AcidMaleMembrane ProteinsMiceMice, KnockoutNeurodegenerative DiseasesNeuronsNeurotoxinsProtein Structure, TertiarySindbis VirusStrokeSynaptic TransmissionConceptsNeuronal excitabilityVirus infectionPostnatal developmentAlters neuronal excitabilityKainate-induced seizuresSpinal cord neuronsIschemia/strokeSindbis virus infectionNeuronal injuryCord neuronsNeuronal deathProtective effectSynaptic activityMouse modelParkinson's diseaseNeuron subtypesNeurotransmitter releasePro-death functionMiceNeuronsSpecific death stimuliDeathSeizuresPossible roleExcitability
2000
Regulation of Synaptic Stability by Bcl‐2 Family Proteins
Kaczmarek L, Jonas E. Regulation of Synaptic Stability by Bcl‐2 Family Proteins. CNS Neuroscience & Therapeutics 2000, 6: 30-31. DOI: 10.1111/j.1527-3458.2000.tb00175.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
1999
Prolonged Activation of Mitochondrial Conductances During Synaptic Transmission
Jonas E, Buchanan J, Kaczmarek L. Prolonged Activation of Mitochondrial Conductances During Synaptic Transmission. Science 1999, 286: 1347-1350. PMID: 10558987, DOI: 10.1126/science.286.5443.1347.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsCalciumCalcium ChannelsDecapodiformesElectric ConductivityElectric StimulationIntracellular MembranesIon ChannelsIon TransportMicroscopy, ElectronMitochondriaPatch-Clamp TechniquesPorinsPresynaptic TerminalsSynaptic TransmissionTime FactorsVoltage-Dependent Anion ChannelsConceptsChannel activityIon channel activityMitochondrial membraneOnly organellesIntracellular organellesIntact cellsIon channelsMitochondriaOrganellesLarge conductanceTens of secondsPresynaptic terminalsIon transportSynaptic transmissionSynaptic stimulationConductanceElectron microscopyPatch-clamp techniqueMembraneActivityCellsActivationSquidStimulation
1997
Giga-Ohm Seals on Intracellular Membranes: A Technique for Studying Intracellular Ion Channels in Intact Cells
Jonas E, Knox R, Kaczmarek L. Giga-Ohm Seals on Intracellular Membranes: A Technique for Studying Intracellular Ion Channels in Intact Cells. Neuron 1997, 19: 7-13. PMID: 9247259, DOI: 10.1016/s0896-6273(00)80343-8.Peer-Reviewed Original ResearchConceptsGiga-ohm sealsIntracellular membranesIntact cellsIntracellular ion channelsMembrane ion channel activityIon channel activityConventional patch clampingOrganelle membranesPlasma membraneInternal organellesInternal membranesInternal organelles membraneCell typesIon channelsChannel activityConfocal imagingInositol trisphosphateLipophilic fluorescent dyeMembranePatch clampingConcentric electrode arrangementPatch-clamp techniqueCellsIntact neuronsOrganellesRegulation by insulin of a unique neuronal Ca2+ pool and of neuropeptide secretion
Jonas E, Knox R, Smith T, Wayne N, Connor J, Kaczmarek L. Regulation by insulin of a unique neuronal Ca2+ pool and of neuropeptide secretion. Nature 1997, 385: 343-346. PMID: 9002519, DOI: 10.1038/385343a0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzoquinonesCalciumCalcium ChannelsCells, CulturedCyclic AMPEndoplasmic ReticulumHeparinInositol 1,4,5-TrisphosphateInositol 1,4,5-Trisphosphate ReceptorsInsulinInvertebrate HormonesLactams, MacrocyclicNeuronsNeuropeptidesProtein-Tyrosine KinasesQuinonesReceptors, Cytoplasmic and NuclearRifabutinThapsigarginConceptsIntracellular Ca2Neuropeptide secretionSpontaneous action potentialsEffect of insulinSecretion of neuropeptidesTyrosine kinase receptorsAcute riseBag cell neuronsDistal tipNeuronal dischargeNeuronal Ca2Distinct intracellular poolsCell neuronsAction potentialsCyclic AMP analogueInsulinNeuropeptidesInsulin receptorKinase receptorsSecretionPresumed siteNeuronsIntracellular poolMitochondrial Ca2Receptors
1996
Ca2+ influx and activation of a cation current are coupled to intracellular Ca2+ release in peptidergic neurons of Aplysia californica.
Knox RJ, Jonas EA, Kao LS, Smith PJ, Connor JA, Kaczmarek LK. Ca2+ influx and activation of a cation current are coupled to intracellular Ca2+ release in peptidergic neurons of Aplysia californica. The Journal Of Physiology 1996, 494: 627-639. PMID: 8865062, PMCID: PMC1160665, DOI: 10.1113/jphysiol.1996.sp021520.Peer-Reviewed Original ResearchConceptsBag cell neuronsCell neuronsThapsigargin-sensitive Ca2Cation currentReversal potentialVoltage-activated Ba2Non-selective cation currentAplysia californicaApparent reversal potentialSteady-state Ca2Thapsigargin-induced elevationMin. 3Endoplasmic reticulum Ca2Voltage-clamp experimentsMicroM tetrodotoxinPeptidergic neuronsIntact gangliaAbdominal ganglionExtracellular Ca2Intracellular Ca2Intracellular storesBAPTA-AMSmall depolarizationBasal levelsNeuronsRegulation of potassium channels by protein kinases
Jonas E, Kaczmarek L. Regulation of potassium channels by protein kinases. Current Opinion In Neurobiology 1996, 6: 318-323. PMID: 8794088, DOI: 10.1016/s0959-4388(96)80114-0.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsInsulin receptor in Aplysia neurons: characterization, molecular cloning, and modulation of ion currents
Jonas E, Knox R, Kaczmarek L, Schwartz J, Solomon D. Insulin receptor in Aplysia neurons: characterization, molecular cloning, and modulation of ion currents. Journal Of Neuroscience 1996, 16: 1645-1658. PMID: 8774433, PMCID: PMC6578688, DOI: 10.1523/jneurosci.16-05-01645.1996.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAmino Acid SequenceAnimalsAplysiaBase SequenceCalcium ChannelsCloning, MolecularDNA, ComplementaryElectrophysiologyImmunohistochemistryInsulinIon ChannelsMolecular ProbesMolecular Sequence DataNeuronsPotassium ChannelsProtein-Tyrosine KinasesReceptor, InsulinTissue DistributionConceptsBag cell neuronsInsulin receptorInsulin-like peptidesImmunocytochemical staining showCell neuronsTyrosine kinase receptorsVertebrate insulinsMolecular cloningHerbimycin ATyrosine residuesTyrosine kinaseKinase receptorsInsulin-like growth factor-1Factor 1Staining showsVoltage-clamped neuronsVoltage-dependent Ca2Growth factor-1Aplysia californicaAplysia neuronsNervous systemReceptorsAction potentialsNeuronsInsulin
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