2023
Molecular mechanism of hyperactivation conferred by a truncation of TRPA1
Bali A, Schaefer S, Trier I, Zhang A, Kabeche L, Paulsen C. Molecular mechanism of hyperactivation conferred by a truncation of TRPA1. Nature Communications 2023, 14: 2867. PMID: 37208332, PMCID: PMC10199097, DOI: 10.1038/s41467-023-38542-1.Peer-Reviewed Original ResearchConceptsChannel sensitizationPlasma membraneHeterologous cellsGenetic analysisMolecular mechanismsBiochemical assaysHeteromeric channelsNonsense mutationPhysiological impactMutantsAgonist sensitivityCalcium permeabilityEnergetic barrierSubunitsTRPA1MutationsTractable mechanismMechanismHyperactivationMembraneCellsActivationAssaysGatingTruncation
2020
Irritant-evoked activation and calcium modulation of the TRPA1 receptor
Zhao J, Lin King JV, Paulsen CE, Cheng Y, Julius D. Irritant-evoked activation and calcium modulation of the TRPA1 receptor. Nature 2020, 585: 141-145. PMID: 32641835, PMCID: PMC7483980, DOI: 10.1038/s41586-020-2480-9.Peer-Reviewed Original ResearchConceptsPrimary afferent nerve fibersTRP channel subtypesAfferent nerve fibersIon channel TRPA1Inflammatory painIrritant receptorsMetabotropic receptorsTRPA1 receptorsCytoplasmic second messengersNerve fibersChannel subtypesCalcium permeabilityCalcium modulationTRPA1 regulationTRPA1Environmental toxicantsFunctional couplingReceptorsPainItchExogenous agentsAttractive targetIrritantsActivationSecond messenger
2017
A Gate Hinge Controls the Epithelial Calcium Channel TRPV5
van der Wijst J, Leunissen EH, Blanchard MG, Venselaar H, Verkaart S, Paulsen CE, Bindels RJ, Hoenderop JG. A Gate Hinge Controls the Epithelial Calcium Channel TRPV5. Scientific Reports 2017, 7: 45489. PMID: 28374795, PMCID: PMC5379628, DOI: 10.1038/srep45489.Peer-Reviewed Original ResearchConceptsEpithelial calcium channel TRPV5Detailed molecular insightStructure-function analysisSite-directed mutagenesisChannel gating mechanismCalcium channel TRPV5TRP channel familyCarboxy terminusDepth structure-function analysisFunctional crosstalkGlycine residueHomology modelingMolecular insightsChannel familyCell deathPermeation pathwayChannel functionChannel TRPV5Increased cell deathNovel insightsIntracellular poresGating mechanismFlexible linkerPore regionTRPV5