2023
Mephedrone induces partial release at human dopamine transporters but full release at human serotonin transporters
Mayer F, Niello M, Bulling S, Zhang Y, Li Y, Kudlacek O, Holy M, Kooti F, Sandtner W, Rudnick G, Schmid D, Sitte H. Mephedrone induces partial release at human dopamine transporters but full release at human serotonin transporters. Neuropharmacology 2023, 240: 109704. PMID: 37703919, DOI: 10.1016/j.neuropharm.2023.109704.Peer-Reviewed Original ResearchSerotonin transporterCarrier-mediated releaseProtein kinase C inhibitor GF109203X.Human embryonic kidney 293Empathogenic effectsAbuse liabilityGreater efficacyElectrophysiological recordingsDopamine transporterHuman DATReverse transportEntactogenic effectsStimulating propertiesHuman serotonin transporterHuman dopamine transporterMephedroneDopamineMolecular mechanismsHDATReleaserTransportersHigh-affinity transporterDATReleasePrevious studiesSLC6 neurotransmitter transporter family in GtoPdb v.2023.1
Bröer S, Rudnick G. SLC6 neurotransmitter transporter family in GtoPdb v.2023.1. IUPHAR/BPS Guide To Pharmacology CITE 2023, 2023 DOI: 10.2218/gtopdb/f144/2023.1.Peer-Reviewed Original ResearchSolute carrier family 6Transporter familyNeurotransmitter transporter familyDependent neurotransmitter transportersAmino acid transportersDependent amino acid transporterNSS transportersTM segmentsPlasma membraneNeurotransmitter transportersAcid transportersFamily 6Neutral amino acidsAmino acidsTransportersStructural motifsGtoPdb v.LeuTAeolicusSubfamiliesFamilyLeuTAaMembersMotifCrystal structure
2019
Serotonin transport in the 21st century
Rudnick G, Sandtner W. Serotonin transport in the 21st century. The Journal Of General Physiology 2019, 151: 1248-1264. PMID: 31570504, PMCID: PMC6829555, DOI: 10.1085/jgp.201812066.Peer-Reviewed Original ResearchSLC6 neurotransmitter transporter family (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Bröer S, Rudnick G. SLC6 neurotransmitter transporter family (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database. IUPHAR/BPS Guide To Pharmacology CITE 2019, 2019 DOI: 10.2218/gtopdb/f144/2019.4.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsSolute carrier family 6Transporter familyNeurotransmitter transporter familyDependent neurotransmitter transportersAmino acid transportersDependent amino acid transporterNSS transportersTM segmentsPlasma membraneNeurotransmitter transportersAcid transportersFamily 6Neutral amino acidsIUPHAR/BPS GuideAmino acidsTransportersStructural motifsLeuTAeolicusSubfamiliesFamilyPharmacology DatabaseLeuTAaMembersMotif
2018
Structural elements required for coupling ion and substrate transport in the neurotransmitter transporter homolog LeuT
Zhang YW, Tavoulari S, Sinning S, Aleksandrova AA, Forrest LR, Rudnick G. Structural elements required for coupling ion and substrate transport in the neurotransmitter transporter homolog LeuT. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e8854-e8862. PMID: 30181291, PMCID: PMC6156673, DOI: 10.1073/pnas.1716870115.Peer-Reviewed Original ResearchConceptsTransporter domainConformational changesOpen stateSodium symporter familyIon-substrate couplingTransmembrane ion gradientsSymporter familyNSS transportersSubstrate bindingLeuTIntracellular substratesCysteine accessibilitySubstrate transportAccessibility of substrateTyrosine residuesConformational responseNa2 siteUncoupled movementIon gradientsExtracellular pathwaysMechanistic componentsTransportersProteinTransport of ionsBinding
2013
How do transporters couple solute movements?
Rudnick G. How do transporters couple solute movements? Molecular Membrane Biology 2013, 30: 355-359. PMID: 24147977, PMCID: PMC4077868, DOI: 10.3109/09687688.2013.842658.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2011
Cytoplasmic Permeation Pathway of Neurotransmitter Transporters
Rudnick G. Cytoplasmic Permeation Pathway of Neurotransmitter Transporters. Biochemistry 2011, 50: 7462-7475. PMID: 21774491, PMCID: PMC3164596, DOI: 10.1021/bi200926b.Peer-Reviewed Original ResearchConceptsCytoplasmic permeation pathwaysBacterial amino acid transporter LeuTNeurotransmitter transportersPermeation pathwayKingdoms of lifeMammalian serotonin transporterHigh-resolution crystal structuresFour-helix bundleRecent high-resolution crystal structureSubsequent crystal structureStructural repeatsLeuT structureProtein familyCommon structural featuresSolute transportersRelated proteinsLarge structural familyCytoplasmic oneConformational changesSubstrate siteFirst structureBiological membranesTransportersLeuTExtracellular pathways
2010
Reconstructing a Chloride-binding Site in a Bacterial Neurotransmitter Transporter Homologue*
Tavoulari S, Rizwan AN, Forrest LR, Rudnick G. Reconstructing a Chloride-binding Site in a Bacterial Neurotransmitter Transporter Homologue*. Journal Of Biological Chemistry 2010, 286: 2834-2842. PMID: 21115480, PMCID: PMC3024779, DOI: 10.1074/jbc.m110.186064.Peer-Reviewed Original ResearchConceptsChloride-binding siteConformational changesAdjacent binding sitesSingle point mutationProkaryotic homologuesSubstrate translocationIon-binding sitesTransporter homologueTransport proteinsNeurotransmitter transportersNeurotransmitter transportPoint mutationsBinding sitesHomologuesProteinMutationsCl(-) bindsDirect evidenceTherapeutic drugsSitesDependent formTranslocationTransportersBindsResidues
2009
Ligand Effects on Cross-linking Support a Conformational Mechanism for Serotonin Transport*
Tao Z, Zhang YW, Agyiri A, Rudnick G. Ligand Effects on Cross-linking Support a Conformational Mechanism for Serotonin Transport*. Journal Of Biological Chemistry 2009, 284: 33807-33814. PMID: 19837674, PMCID: PMC2797150, DOI: 10.1074/jbc.m109.071977.Peer-Reviewed Original ResearchConceptsN-terminal cyanogen bromide fragmentGamma-aminobutyric acid transporterCyanogen bromide fragmentsTransmembrane 1Cysteine residuesMutagenesis strategyAcid transportersConformational mechanismSerotonin transportCysteineCorresponding positionDisulfide CrossTransportersSynaptic cleftResiduesSame molecule
2008
Mechanism for alternating access in neurotransmitter transporters
Forrest LR, Zhang YW, Jacobs MT, Gesmonde J, Xie L, Honig BH, Rudnick G. Mechanism for alternating access in neurotransmitter transporters. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 10338-10343. PMID: 18647834, PMCID: PMC2480614, DOI: 10.1073/pnas.0804659105.Peer-Reviewed Original ResearchConceptsNeurotransmitter transportersMammalian neurotransmitter transportersMammalian serotonin transporterTransmembrane helix 1Bacterial homologueIon-binding sitesTransporter familyExtensive mutagenesisHelix 1Similar repeatsLeuTConformational changesSerotonin transporterRepeatsAlternate conformationConformational differencesExtracellular pathwaysCytoplasmTransportersExtracellular spaceCysteine reagentCrystal structureConformationPathwayAccessibility measurements
2002
Chemical Modification Strategies for Structure‐Function Studies
Rudnick G. Chemical Modification Strategies for Structure‐Function Studies. 2002, 125-141. DOI: 10.1002/0471434043.ch8.ChaptersTransmembrane domainConformational changesPolytopic membrane proteinsStructure-function studiesMembrane proteinsTransporter proteinsReactive residuesLipid bilayersProteinTransportersExternal faceExternal loopChemical modification strategiesDomainChemical modificationSubstrateCysteineResiduesSitesMembraneModificationBilayers
2001
The NH2-terminus of Norepinephrine Transporter Contains a Basolateral Localization Signal for Epithelial Cells
Gu H, Wu X, Giros B, Caron M, Caplan M, Rudnick G. The NH2-terminus of Norepinephrine Transporter Contains a Basolateral Localization Signal for Epithelial Cells. Molecular Biology Of The Cell 2001, 12: 3797-3807. PMID: 11739781, PMCID: PMC60756, DOI: 10.1091/mbc.12.12.3797.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell LineCell PolarityDogsDopamine Plasma Membrane Transport ProteinsEpithelial CellsHumansMembrane GlycoproteinsMembrane Transport ProteinsMiceMicroscopy, ConfocalMolecular Sequence DataMutagenesis, Site-DirectedNerve Tissue ProteinsNorepinephrine Plasma Membrane Transport ProteinsProtein Sorting SignalsSequence AlignmentSymportersConceptsBasolateral localization signalLocalization signalDileucine motifPlasma membraneBasolateral localizationOverall amino acid sequence identityAmino acid sequence identityTerminal regionMDCK cellsApical plasma membraneBasolateral membraneEpithelial cellsSequence identityApical localizationChimeric proteinTransport assaysTransporter localizationAmino acidsApical membraneNorepinephrine transporterTransportersCorresponding sequenceDopamine transporterSame mutationMembrane
2000
Functional Role of Critical Stripe Residues in Transmembrane Span 7 of the Serotonin Transporter EFFECTS OF Na+, Li+, AND METHANETHIOSULFONATE REAGENTS*
Kamdar G, Penado K, Rudnick G, Stephan M. Functional Role of Critical Stripe Residues in Transmembrane Span 7 of the Serotonin Transporter EFFECTS OF Na+, Li+, AND METHANETHIOSULFONATE REAGENTS*. Journal Of Biological Chemistry 2000, 276: 4038-4045. PMID: 11058600, DOI: 10.1074/jbc.m008483200.Peer-Reviewed Original ResearchConceptsCys-109Methanethiosulfonate reagentsWater-filled poresNative cysteine residuesCysteine-containing mutantsExtracellular loop 1Close-contact regionThree-dimensional structureCysteine residuesTranslocation mechanismControl mutantsAlpha-helixMTSEA-biotinResidue positionsCysteine substitutionsLoop 1Conformational changesMTS reagentsFunctional roleMutantsIon bindingResiduesTransportersIon dependenceSerotonin transporter
1999
The Role of External Loop Regions in Serotonin Transport LOOP SCANNING MUTAGENESIS OF THE SEROTONIN TRANSPORTER EXTERNAL DOMAIN*
Smicun Y, Campbell S, Chen M, Gu H, Rudnick G. The Role of External Loop Regions in Serotonin Transport LOOP SCANNING MUTAGENESIS OF THE SEROTONIN TRANSPORTER EXTERNAL DOMAIN*. Journal Of Biological Chemistry 1999, 274: 36058-36064. PMID: 10593887, DOI: 10.1074/jbc.274.51.36058.Peer-Reviewed Original ResearchConceptsChimeric transportersWild type SERTExternal loop 4High affinity cocaine analogSubsequent conformational changesExternal loop regionsTransmembrane segmentsInitial binding stepScanning mutagenesisWild typeExternal loopLigand bindingSerotonin transporterMutantsConformational changesLoop 4Loop regionConformational flexibilityTransportersCorresponding sequenceBinding stepExternal domainNorepinephrine transporterActivity 5NET substrate
1998
Critical Amino Acid Residues in Transmembrane Span 7 of the Serotonin Transporter Identified by Random Mutagenesis*
Penado K, Rudnick G, Stephan M. Critical Amino Acid Residues in Transmembrane Span 7 of the Serotonin Transporter Identified by Random Mutagenesis*. Journal Of Biological Chemistry 1998, 273: 28098-28106. PMID: 9774428, DOI: 10.1074/jbc.273.43.28098.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBiological TransportCarrier ProteinsMembrane GlycoproteinsMembrane Transport ProteinsModels, MolecularMolecular Sequence DataMutagenesisNerve Tissue ProteinsProtein ConformationRatsSerotoninSerotonin Plasma Membrane Transport ProteinsStructure-Activity RelationshipConceptsAmino acid residuesRandom mutagenesisAcid residuesTransport activityCritical amino acid residuesRat brain serotonin transporterCritical residuesTransport cycleWild typeNonconservative mutationsStructural predictionsTransporter functionLater stepsMutationsSerotonin transporterResiduesMutagenesisHydrophobic substitutionsTyr-385TransportersMutantsActivitySubstitutionNearby positionsBioenergetics of Neurotransmitter Transport
Rudnick G. Bioenergetics of Neurotransmitter Transport. Journal Of Bioenergetics And Biomembranes 1998, 30: 173-185. PMID: 9672239, DOI: 10.1023/a:1020573325823.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSynaptic vesicle membranePlasma membrane transportersRecycling of neurotransmittersGene familyVesicle lumenPlasma membraneMembrane transportersNeurotransmitter transportersVesicle membraneNeurotransmitter transportVesicular transportersAmino acidsTransportersCoupling stoichiometryDownhill movementCytoplasmEssential componentUphill transportFamilyMembraneEffluxBioenergeticsImportant drugsProteinInflux
1997
Placental biogenic amine transporters: cloning and expression
Padbury J, Tseng Y, McGonnigal B, Penado K, Stephan M, Rudnick G. Placental biogenic amine transporters: cloning and expression. Brain Research 1997, 45: 163-168. PMID: 9105686, DOI: 10.1016/s0169-328x(96)00309-9.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBrainCarrier ProteinsCell MembraneCloning, MolecularFemaleHumansMembrane GlycoproteinsMembrane Transport ProteinsMolecular Sequence DataNerve Tissue ProteinsNeuronsPlacentaPregnancyProtein BiosynthesisRecombinant ProteinsSequence Homology, Amino AcidSequence Homology, Nucleic AcidSerotoninSerotonin Plasma Membrane Transport ProteinsSheepAn Extracellular Loop Region of the Serotonin Transporter May Be Involved in the Translocation Mechanism †
Stephan M, Chen M, Penado K, Rudnick G. An Extracellular Loop Region of the Serotonin Transporter May Be Involved in the Translocation Mechanism †. Biochemistry 1997, 36: 1322-1328. PMID: 9063880, DOI: 10.1021/bi962150l.Peer-Reviewed Original ResearchConceptsLarge extracellular loopChimeric transportersWild typeWild type SERTExtracellular loopCocaine analog 2beta-carbomethoxy-3betaCell surface biotinylationWild-type levelsSubstrate translocationExtracellular loop regionSurface biotinylationTranslocation mechanismSerotonin transporterHomologous familyType levelsConformational changesLoop regionRestriction sitesTransportersPoor expressionSubstituted regionsSynaptic cleftDrug bindingSame specificityHigh affinityExternal Cysteine Residues in the Serotonin Transporter †
Chen J, Liu-Chen S, Rudnick G. External Cysteine Residues in the Serotonin Transporter †. Biochemistry 1997, 36: 1479-1486. PMID: 9063896, DOI: 10.1021/bi962256g.Peer-Reviewed Original ResearchConceptsTransport activityMTS reagentsCysteine residuesWild typeWild-type transporterSecond external loopTransient expression systemSurface expressionRat serotonin transporterExternal cysteine residuesHydropathy analysisMutant transportersType transporterDouble mutantExpression systemMethanethiosulfonate reagentsLigand bindingSerotonin transporterMutantsExtracellular loopHeLa cellsDisulfide bondsPartial activityTransportersSerine
1996
Cell-specific Sorting of Biogenic Amine Transporters Expressed in Epithelial Cells*
Gu H, Ahn J, Caplan M, Blakely R, Levey A, Rudnick G. Cell-specific Sorting of Biogenic Amine Transporters Expressed in Epithelial Cells*. Journal Of Biological Chemistry 1996, 271: 18100-18106. PMID: 8663573, DOI: 10.1074/jbc.271.30.18100.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiogenic AminesBiological TransportCarrier ProteinsCell CompartmentationCell MembraneCell PolarityCells, CulturedDogsDopamineDopamine Plasma Membrane Transport ProteinsEpithelial CellsHumansImmunohistochemistryMembrane GlycoproteinsMembrane Transport ProteinsNerve Tissue ProteinsNorepinephrineNorepinephrine Plasma Membrane Transport ProteinsRatsRecombinant ProteinsSerotoninSerotonin Plasma Membrane Transport ProteinsSymportersConceptsMadin-Darby canine kidneyMDCK cellsLLC-PK1 cellsNeurotransmitter transportersCell surface biotinylationConfocal immunofluorescence microscopyBasolateral membraneCell-specific mechanismsEpithelial cellsBiogenic amine transportersMembrane proteinsSurface biotinylationCDNA encodingHuman DA transporterAmine transportersImmunofluorescence microscopyBiotinylating reagentTransportersPermeable filter supportsApical surfaceImmunocytochemistry resultsBasolateral mediumSurface expressionApical sideDA transporter