2016
Control of serotonin transporter phosphorylation by conformational state
Zhang YW, Turk BE, Rudnick G. Control of serotonin transporter phosphorylation by conformational state. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e2776-e2783. PMID: 27140629, PMCID: PMC4878475, DOI: 10.1073/pnas.1603282113.Peer-Reviewed Original ResearchConceptsTransmembrane helix 5Cytoplasmic permeation pathwaysOutward open conformationIntact rat basophilic leukemia cellsCGMP-dependent phosphorylationInhibition of phosphorylationTM5 helicesTransporter phosphorylationSERT regulationOutward openingCysteine residuesHelix 5Open conformationCytoplasmic endHuman SERTPhosphorylationPermeation pathwayConformational statesHeLa cellsRat basophilic leukemia cellsBasophilic leukemia cellsSERT activityExocytotic releaseLeukemia cellsMutations
2013
Isoforms of the neuronal glutamate transporter gene, SLC1A1/EAAC1, negatively modulate glutamate uptake: relevance to obsessive-compulsive disorder
Porton B, Greenberg B, Askland K, Serra L, Gesmonde J, Rudnick G, Rasmussen S, Kao H. Isoforms of the neuronal glutamate transporter gene, SLC1A1/EAAC1, negatively modulate glutamate uptake: relevance to obsessive-compulsive disorder. Translational Psychiatry 2013, 3: e259-e259. PMID: 23695234, PMCID: PMC3669922, DOI: 10.1038/tp.2013.35.Peer-Reviewed Original ResearchConceptsExcellent candidate geneObsessive-compulsive disorderNeuronal glutamate transporterGenomic levelInternal promoterCandidate genesPartial colocalizationTransporter geneGene expressionGenetic studiesGlutamate uptakeEAAC1 transporterPrimary promoterEAAC1 proteinGlutamate transporter geneGenesPhysiological regulatorIsoformsTranscriptsExon 2Glutamate transportersGlutamatergic gene expressionPromoterPotential clinical utilityNeuronal glutamate transporter gene
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 measurementsInvolvement of serotonin transporter extracellular loop 1 in serotonin binding and transport
Mao Y, Mao Y, Mathewson L, Mao Y, Mathewson L, Gesmonde J, Sato Y, Mao Y, Mathewson L, Gesmonde J, Sato Y, Holy M, Sitte H, Rudnick G. Involvement of serotonin transporter extracellular loop 1 in serotonin binding and transport. Molecular Membrane Biology 2008, 25: 115-127. PMID: 18307099, PMCID: PMC4510095, DOI: 10.1080/09687680701633257.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBiological TransportCell MembraneHeLa CellsHumansIndicators and ReagentsKineticsLigandsMesylatesMolecular Sequence DataMutant ProteinsProtein Structure, TertiaryRatsSequence DeletionSerotoninSerotonin Plasma Membrane Transport ProteinsStructure-Activity Relationship
2001
A Lithium-induced Conformational Change in Serotonin Transporter Alters Cocaine Binding, Ion Conductance, and Reactivity of Cys-109*
Ni Y, Chen J, Androutsellis-Theotokis A, Huang C, Moczydlowski E, Rudnick G. A Lithium-induced Conformational Change in Serotonin Transporter Alters Cocaine Binding, Ion Conductance, and Reactivity of Cys-109*. Journal Of Biological Chemistry 2001, 276: 30942-30947. PMID: 11408487, DOI: 10.1074/jbc.m104653200.Peer-Reviewed Original Research
2000
Oligomerization of serotonin transporter and its functional consequences
Kilic F, Rudnick G. Oligomerization of serotonin transporter and its functional consequences. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 3106-3111. PMID: 10716733, PMCID: PMC16200, DOI: 10.1073/pnas.97.7.3106.Peer-Reviewed Original Research
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 substrateMolecular cloning, expression and characterization of a bovine serotonin transporter1The sequence reported in this paper has been deposited in the GenBank data base (accession number AF119122).1
Mortensen O, Kristensen A, Rudnick G, Wiborg O. Molecular cloning, expression and characterization of a bovine serotonin transporter1The sequence reported in this paper has been deposited in the GenBank data base (accession number AF119122).1. Brain Research 1999, 71: 120-126. PMID: 10407194, DOI: 10.1016/s0169-328x(99)00178-3.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCarrier ProteinsCattleCitalopramCloning, MolecularDesipramineFemaleFluoxetineHeLa CellsHumansImipramineKineticsMembrane GlycoproteinsMembrane Transport ProteinsMolecular Sequence DataNerve Tissue ProteinsN-Methyl-3,4-methylenedioxyamphetamineOrgan SpecificityParoxetinePhylogenyPregnancyRatsRecombinant ProteinsReverse Transcriptase Polymerase Chain ReactionSequence AlignmentSequence Homology, Amino AcidSerotoninSerotonin Plasma Membrane Transport ProteinsTransfectionConceptsSerotonin transporterHuman serotonin transporterExpression of SERTAdrenal glandBrain stemParathyroid glandsPharmacological profileBone marrowThyroid glandSmall intestinePharmacological targetsRT-PCR amplificationDecreased sensitivityExtracellular fluidGlandAmino acid differencesBiogenic aminesNeurotransmitter transportersDependent neurotransmitter transportersImportant antidepressantsAcid differencesDifferent tissuesAntidepressantsParoxetineDesipramine
1997
An 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
1994
Human norepinephrine transporter. Biosynthetic studies using a site-directed polyclonal antibody.
Melikian H, McDonald J, Gu H, Rudnick G, Moore K, Blakely R. Human norepinephrine transporter. Biosynthetic studies using a site-directed polyclonal antibody. Journal Of Biological Chemistry 1994, 269: 12290-12297. PMID: 8163533, DOI: 10.1016/s0021-9258(17)32714-x.Peer-Reviewed Original ResearchAnimalsAntibodiesCarrier ProteinsCell LineCysteineElectrophoresis, Polyacrylamide GelEnzyme-Linked Immunosorbent AssayFluorescent Antibody TechniqueHeLa CellsHumansImmunoblottingKineticsMethionineMolecular WeightNorepinephrineNorepinephrine Plasma Membrane Transport ProteinsRabbitsSulfur RadioisotopesSymportersTransfectionTunicamycin
1992
Expression of a cloned gamma-aminobutyric acid transporter in mammalian cells.
Keynan S, Suh Y, Kanner B, Rudnick G. Expression of a cloned gamma-aminobutyric acid transporter in mammalian cells. Biochemistry 1992, 31: 1974-9. PMID: 1536839, DOI: 10.1021/bi00122a011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportCarrier ProteinsChloridesCloning, MolecularDNAGABA Plasma Membrane Transport ProteinsGamma-Aminobutyric AcidGene ExpressionGenetic VectorsHeLa CellsHumansKineticsL CellsMembrane ProteinsMembrane Transport ProteinsMiceNerve Tissue ProteinsOrganic Anion TransportersPlasmidsPrecipitin TestsRatsSodiumTransfectionTunicamycinXenopusConceptsMammalian cellsGABA transportMouse Ltk- cellsT7 RNA polymerasePlasma membrane vesiclesL cellsApparent molecular massGABA transporterSynaptic plasma membrane vesiclesGamma-aminobutyric acid transporterPresence of tunicamycinEukaryotic expression vectorRNA polymeraseTransient expressionExpression vectorAcid transportersMembrane vesiclesStable expressionLtk- cellsFunctional expressionGAT-1Molecular massHeLa cellsTransportersTransfection
1991
Vaccinia-T7 RNA polymerase expression system: Evaluation for the expression cloning of plasma membrane transporters
Blakely R, Clark J, Rudnick G, Amara S. Vaccinia-T7 RNA polymerase expression system: Evaluation for the expression cloning of plasma membrane transporters. Analytical Biochemistry 1991, 194: 302-308. PMID: 1862934, DOI: 10.1016/0003-2697(91)90233-j.Peer-Reviewed Original Research