2023
Genetic, electrophysiological, and pathological studies on patients with SCN9A‐related pain disorders
Yuan J, Cheng X, Matsuura E, Higuchi Y, Ando M, Hashiguchi A, Yoshimura A, Nakachi R, Mine J, Taketani T, Maeda K, Kawakami S, Kira R, Tanaka S, Kanai K, Dib‐Hajj F, Dib‐Hajj S, Waxman S, Takashima H. Genetic, electrophysiological, and pathological studies on patients with SCN9A‐related pain disorders. Journal Of The Peripheral Nervous System 2023, 28: 597-607. PMID: 37555797, DOI: 10.1111/jns.12590.Peer-Reviewed Original ResearchConceptsParoxysmal extreme pain disorderPainful peripheral neuropathyPain disordersSCN9A mutationsPeripheral neuropathyNovel SCN9A mutationsVoltage-gated sodium channel Nav1.7Sodium channel Nav1.7Steady-state fast inactivationGene panel sequencingPatch-clamp analysisAutonomic neuropathyNeuropathic painSCN9A geneClinical featuresUnderlying pathogenesisPathological studiesPatientsChannel Nav1.7EM phenotypePhenotypic spectrumNeuropathyNav1.7 channelsPatch-clamp systemElectrophysiological analysis
2019
Altered allostery of the left flipper domain underlies the weak ATP response of rat P2X5 receptors
Sun L, Liu Y, Wang J, Huang L, Yang Y, Cheng X, Fan Y, Zhu M, Liang H, Tian Y, Wang H, Guo C, Yu Y. Altered allostery of the left flipper domain underlies the weak ATP response of rat P2X5 receptors. Journal Of Biological Chemistry 2019, 294: 19589-19603. PMID: 31727741, PMCID: PMC6926468, DOI: 10.1074/jbc.ra119.009959.Peer-Reviewed Original ResearchConceptsFuture transgenic studiesFull-length variantATP responseTransmembrane domainTransgenic studiesMammalian speciesP2X5 receptorsAllosteryPathological functionsSingle replacementSingle-channel recordingsSkeletal muscleExon 10Molecular modelingFunctional subtypesATPResiduesNervous systemP2X5ReceptorsDomainMammalsSpeciesTM2Lack of knowledge
2018
Druggable negative allosteric site of P2X3 receptors
Wang J, Wang Y, Cui W, Huang Y, Yang Y, Liu Y, Zhao W, Cheng X, Sun W, Cao P, Zhu M, Wang R, Hattori M, Yu Y. Druggable negative allosteric site of P2X3 receptors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 4939-4944. PMID: 29674445, PMCID: PMC5948998, DOI: 10.1073/pnas.1800907115.Peer-Reviewed Original ResearchConceptsAllosteric siteNegative allosteric siteDruggable allosteric sitesG protein-coupled receptorsAllosteric modulationLeft flipperProtein-coupled receptorsNew drug targetsDorsal fin domainLB domainsClinical trialsP2X receptorsAllosteric changesAllosteric inhibitorsChannel mutantsDrug targetsPhase II clinical trialFunctional studiesFin domainRefractory chronic coughIdiopathic pulmonary fibrosisIon channelsLower bodyX-ray crystallographyNegative allosteric modulationNav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner
Li Y, Zhu T, Yang H, Dib-Hajj S, Waxman S, Yu Y, Xu TL, Cheng X. Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner. Molecular Pain 2018, 14: 1744806918782229. PMID: 29790812, PMCID: PMC6024516, DOI: 10.1177/1744806918782229.Peer-Reviewed Original ResearchConceptsND7/23 cellsDRG neuron excitabilityModulation of Nav1.7New pain therapeuticsVoltage-gated sodium channel Nav1.7Fyn kinaseWhole-cell recordingsSodium channel Nav1.7Elevated protein expressionCell type-specific modulationHuman embryonic kidney 293 cellsTyrosine kinasePain disordersEmbryonic kidney 293 cellsPain therapeuticsNeuron excitabilityPain perceptionMutant channelsChannel Nav1.7Kidney 293 cellsNav1.7HEK-293 cellsNav1.7 channelsCell type-dependent mannerType-dependent manner
2017
N1366S mutation of human skeletal muscle sodium channel causes paramyotonia congenita
Ke Q, Ye J, Tang S, Wang J, Luo B, Ji F, Zhang X, Yu Y, Cheng X, Li Y. N1366S mutation of human skeletal muscle sodium channel causes paramyotonia congenita. The Journal Of Physiology 2017, 595: 6837-6850. PMID: 28940424, PMCID: PMC5685822, DOI: 10.1113/jp274877.Peer-Reviewed Original ResearchIntersubunit physical couplings fostered by the left flipper domain facilitate channel opening of P2X4 receptors
Wang J, Sun L, Cui W, Zhao W, Ma X, Li B, Liu Y, Yang Y, Hu Y, Huang L, Cheng X, Li L, Lu X, Tian Y, Yu Y. Intersubunit physical couplings fostered by the left flipper domain facilitate channel opening of P2X4 receptors. Journal Of Biological Chemistry 2017, 292: 7619-7635. PMID: 28302727, PMCID: PMC5418059, DOI: 10.1074/jbc.m116.771121.Peer-Reviewed Original ResearchFGF13 Selectively Regulates Heat Nociception by Interacting with Nav1.7
Yang L, Dong F, Yang Q, Yang P, Wu R, Wu Q, Wu D, Li C, Zhong Y, Lu Y, Cheng X, Xu F, Chen L, Bao L, Zhang X. FGF13 Selectively Regulates Heat Nociception by Interacting with Nav1.7. Neuron 2017, 93: 806-821.e9. PMID: 28162808, DOI: 10.1016/j.neuron.2017.01.009.Peer-Reviewed Original ResearchConceptsDorsal root gangliaAction potential firingHeat nociceptionFibroblast growth factorDRG neuronsSustained action potential firingTransient receptor potential cation channel V1Intracellular fibroblast growth factorsNoxious heat stimulationNoxious heat stimuliMouse DRG neuronsNociceptive neuronsNociceptive behaviorSodium channel NaRoot gangliaHeat stimuliNociceptionAction potentialsSodium currentHeat stimulationGrowth factorFGF13NeuronsChannel NaCurrent knowledge
2016
Long noncoding RNA glypican 3 (GPC3) antisense transcript 1 promotes hepatocellular carcinoma progression via epigenetically activating GPC3
Zhu X, Yuan J, Zhu T, Li Y, Cheng X. Long noncoding RNA glypican 3 (GPC3) antisense transcript 1 promotes hepatocellular carcinoma progression via epigenetically activating GPC3. The FEBS Journal 2016, 283: 3739-3754. PMID: 27573079, DOI: 10.1111/febs.13839.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAlpha-FetoproteinsAnimalsBiomarkers, TumorCarcinoma, HepatocellularCell Line, TumorDisease ProgressionEpigenesis, GeneticGlypicansHep G2 CellsHeterograftsHistonesHumansLiver NeoplasmsMiceMice, NudePrognosisPromoter Regions, GeneticRNA, AntisenseRNA, Long NoncodingTranscriptional ActivationUp-RegulationConceptsHCC cell proliferationBarcelona Clinic Liver Cancer stageCell proliferationTranscript 1Inhibited HCC cell proliferationLiver Cancer stageHepatocellular carcinoma screeningPotential therapeutic targetXenograft tumor growthHepatocellular carcinoma progressionP300/CBP-associated factorWorse prognosisCarcinoma screeningMicrovascular invasionTumor sizeHCC patientsCancer stageTherapeutic targetHCC progressionTumor growthCarcinoma progressionPotential biomarkersPathophysiological processesHCC tissuesSignificant upregulationExploration of the Peptide Recognition of an Amiloride-sensitive FMRFamide Peptide-gated Sodium Channel*
Niu Y, Yang Y, Liu Y, Huang L, Yang X, Fan Y, Cheng X, Cao P, Hu Y, Li L, Lu X, Tian Y, Yu Y. Exploration of the Peptide Recognition of an Amiloride-sensitive FMRFamide Peptide-gated Sodium Channel*. Journal Of Biological Chemistry 2016, 291: 7571-7582. PMID: 26867576, PMCID: PMC4817185, DOI: 10.1074/jbc.m115.710251.Peer-Reviewed Original ResearchA Highly Conserved Salt Bridge Stabilizes the Kinked Conformation of β2,3-Sheet Essential for Channel Function of P2X4 Receptors*
Zhao W, Sun M, Sun L, Liu Y, Yang Y, Huang L, Fan Y, Cheng X, Cao P, Hu Y, Li L, Tian Y, Wang R, Yu Y. A Highly Conserved Salt Bridge Stabilizes the Kinked Conformation of β2,3-Sheet Essential for Channel Function of P2X4 Receptors*. Journal Of Biological Chemistry 2016, 291: 7990-8003. PMID: 26865631, PMCID: PMC4825005, DOI: 10.1074/jbc.m115.711127.Peer-Reviewed Original Research
2011
CaV1.2 Channel N-terminal Splice Variants Modulate Functional Surface Expression in Resistance Size Artery Smooth Muscle Cells*
Bannister J, Thomas-Gatewood C, Neeb Z, Adebiyi A, Cheng X, Jaggar J. CaV1.2 Channel N-terminal Splice Variants Modulate Functional Surface Expression in Resistance Size Artery Smooth Muscle Cells*. Journal Of Biological Chemistry 2011, 286: 15058-15066. PMID: 21357696, PMCID: PMC3083159, DOI: 10.1074/jbc.m110.182816.Peer-Reviewed Original ResearchConceptsArterial smooth muscle cellsSmooth muscle cellsMuscle cellsSurface expressionIntravascular pressureSmooth muscle-specific expressionArtery smooth muscle cellsDepolarization-induced vasoconstrictionHuman cerebral arteriesWhole-cell currentsReduced surface expressionLarge vasodilationCerebral arteryInflux pathwayVariety of stimuliCardiovascular systemFunctional surface expressionVasodilationProximal N-terminusReduced expressionMuscle-specific expressionE1CAuxiliary subunitsKnockdownPhysiological functions
2007
A Novel CaV1.2 N Terminus Expressed in Smooth Muscle Cells of Resistance Size Arteries Modifies Channel Regulation by Auxiliary Subunits*
Cheng X, Liu J, Asuncion-Chin M, Blaskova E, Bannister J, Dopico A, Jaggar J. A Novel CaV1.2 N Terminus Expressed in Smooth Muscle Cells of Resistance Size Arteries Modifies Channel Regulation by Auxiliary Subunits*. Journal Of Biological Chemistry 2007, 282: 29211-29221. PMID: 17699517, PMCID: PMC2276565, DOI: 10.1074/jbc.m610623200.Peer-Reviewed Original ResearchConceptsExon 1cN-terminusExon 1bAuxiliary subunitsRich N-terminusCysteine-rich N-terminusNovel alternative splicingResistance-size cerebral arteriesPlasma membrane insertionExon 1Arterial myocytesMultiple vascular functionsIsoform-dependent differencesWhole-cell current densityN-terminal variantsAlternative splicingMembrane insertionChannel regulationExon 1AMolecular identityHuman diseasesSubunitsTerminusEntry pathwaySmooth muscle cells