2019
Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1)
Ali SR, Malone TJ, Zhang Y, Prechova M, Kaczmarek LK. Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1). The FASEB Journal 2019, 34: 1591-1601. PMID: 31914597, PMCID: PMC6956700, DOI: 10.1096/fj.201902366r.Peer-Reviewed Original ResearchConceptsProtein phosphatase 1Phosphatase 1Binding of PP1C-terminusCytoplasmic signaling proteinsCytoplasmic C-terminusActin-binding proteinsSlack channelsPKC phosphorylation sitesPhosphoprotein substratesDisease-causing mutationsPhosphorylation sitesSignaling proteinsSlack currentsHuman mutationsSodium-activated potassium channelsPHACTR1Slack genePotassium channelsProteinActinMutationsPatch-clamp recordingsCentral nervous systemMutantsAn Epilepsy-Associated KCNT1 Mutation Enhances Excitability of Human iPSC-Derived Neurons by Increasing Slack KNa Currents
Quraishi IH, Stern S, Mangan KP, Zhang Y, Ali SR, Mercier MR, Marchetto MC, McLachlan MJ, Jones EM, Gage FH, Kaczmarek LK. An Epilepsy-Associated KCNT1 Mutation Enhances Excitability of Human iPSC-Derived Neurons by Increasing Slack KNa Currents. Journal Of Neuroscience 2019, 39: 7438-7449. PMID: 31350261, PMCID: PMC6759030, DOI: 10.1523/jneurosci.1628-18.2019.Peer-Reviewed Original ResearchConceptsSevere epileptic encephalopathyAction potentialsEpileptic encephalopathyFiring rateCurrent-clamp recordingsSodium-activated potassium channelsMaximal firing rateIntensity of firingMean firing rateKCNT1 mutationsCortical neuronsCell-autonomous mechanismsEffective treatmentHuman neuronsPotassium currentActive neuronsNeuronsPotassium channelsCompensatory changesDisease-causing mutationsHyperexcitabilityHuman iPSCEncephalopathyExcitabilityStem cells
2016
Stimulation of Slack K+ Channels Alters Mass at the Plasma Membrane by Triggering Dissociation of a Phosphatase-Regulatory Complex
Fleming MR, Brown MR, Kronengold J, Zhang Y, Jenkins DP, Barcia G, Nabbout R, Bausch AE, Ruth P, Lukowski R, Navaratnam DS, Kaczmarek LK. Stimulation of Slack K+ Channels Alters Mass at the Plasma Membrane by Triggering Dissociation of a Phosphatase-Regulatory Complex. Cell Reports 2016, 16: 2281-2288. PMID: 27545877, PMCID: PMC5123741, DOI: 10.1016/j.celrep.2016.07.024.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBiosensing TechniquesBithionolBridged Bicyclo Compounds, HeterocyclicCell MembraneCerebral CortexFragile X Mental Retardation ProteinGene Expression RegulationHEK293 CellsHumansIon TransportMiceMice, KnockoutMicrofilament ProteinsMutationNerve Tissue ProteinsNeuronsPatch-Clamp TechniquesPhosphorylationPotassium ChannelsPotassium Channels, Sodium-ActivatedPrimary Cell CultureProtein BindingRNA, Small InterferingSignal TransductionThiazolidinesXenopus laevisConceptsProtein phosphatase 1Plasma membraneProtein kinase C.C-terminal residuesPhactr-1Potassium channelsPhosphatase 1Terminal domainSlack channelsHuman mutationsKinase C.Sodium-activated potassium channelsPharmacological activatorsOptical biosensor assayChannel stimulationSlack currentsBiosensor assaysMembraneMutantsPhosphorylationIntellectual disabilityProteinMutationsSevere intellectual disabilityActivatorT Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels
Matza D, Badou A, Klemic KG, Stein J, Govindarajulu U, Nadler MJ, Kinet JP, Peled A, Shapira OM, Kaczmarek LK, Flavell RA. T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels. PLOS ONE 2016, 11: e0147379. PMID: 26815481, PMCID: PMC4729531, DOI: 10.1371/journal.pone.0147379.Peer-Reviewed Original Research
2014
Use of label-free optical biosensors to detect modulation of potassium channels by G-protein coupled receptors.
Fleming MR, Shamah SM, Kaczmarek LK. Use of label-free optical biosensors to detect modulation of potassium channels by G-protein coupled receptors. Journal Of Visualized Experiments 2014, e51307. PMID: 24562095, PMCID: PMC4122194, DOI: 10.3791/51307.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsOptical biosensorPlasma membraneLabel-free optical biosensorProtein-protein interactionsIon channelsChannel-protein interactionsExcitable cell typesReceptor tyrosine kinasesProtein-coupled receptorsLigand-induced changesCell surface receptorsPotassium channelsRegulatory proteinsTyrosine kinaseG proteinsProtein behaviorSodium-activated potassium channelsExogenous labelsPhysiological relevanceCell adhesionLiving cellsCell typesHeteromeric channelsSurface receptors