2024
A complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell–cell contacts
Johnson B, Iuliano M, Lam T, Biederer T, De Camilli P. A complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell–cell contacts. Journal Of Cell Biology 2024, 223: e202311137. PMID: 39158698, PMCID: PMC11334333, DOI: 10.1083/jcb.202311137.Peer-Reviewed Original ResearchConceptsPlasma membraneNon-vesicular lipid transferSites of cell contactC-terminus motifsCell contact-dependent signalsContact-dependent signalingCell-cell contactER/PM junctionsTMEM24ER proteinsPM proteinsSynCAM 1Cell adhesion moleculesCellular functionsLipid transferC2CD2Phospholipid transportLipid transportCell contactProteinAdhesion moleculesCalcium homeostasisCellsFamily membersParalogs
2023
Peripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles
Ganesh S, Lam T, Garcia-Milian R, D'Souza D, Nairn A, Elgert K, Eitan E, Ranganathan M. Peripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles. The World Journal Of Biological Psychiatry 2023, 24: 603-613. PMID: 36994633, PMCID: PMC10471733, DOI: 10.1080/15622975.2023.2197039.Peer-Reviewed Original ResearchConceptsNeuron-derived extracellular vesiclesLabel-free quantification mass spectrometryProteomic studiesCannabis use disorderExtracellular vesiclesMass spectrometry proteomic analysisDifferential proteomic profilesAdapter proteinProteomic analysisPost-synaptic densityPeripheral signatureMolecular basisProteomic profilesProteinMarkers of neuropathologyBrain tissue samplesSynaptic pathologyVesiclesSynaptic integrityImmunoaffinity methodUse disordersFunctional integrityImportant insightsNeuropathologyPilot studyThe C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion
Onuchic L, Padovano V, Schena G, Rajendran V, Dong K, Shi X, Pandya R, Rai V, Gresko N, Ahmed O, Lam T, Wang W, Shen H, Somlo S, Caplan M. The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion. Nature Communications 2023, 14: 1790. PMID: 36997516, PMCID: PMC10063565, DOI: 10.1038/s41467-023-37449-1.Peer-Reviewed Original ResearchConceptsPolycystin-1Nicotinamide nucleotide transhydrogenaseTerminal tailCystic phenotypeAutosomal dominant polycystic kidney diseaseCyst cell proliferationC-terminal domainAmino acid residuesLethal monogenic disorderC-terminal cleavageNucleotide transhydrogenaseAcid residuesMitochondrial functionTransgenic expressionPKD1 geneRedox stateShort fragmentsCell proliferationMonogenic disordersDominant polycystic kidney diseasePolycystic kidney diseaseGene therapy strategiesProteinPhenotypeFragments
2022
Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction
Griffin KN, Walters BW, Li H, Wang H, Biancon G, Tebaldi T, Kaya CB, Kanyo J, Lam TT, Cox AL, Halene S, Chung JJ, Lesch BJ. Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction. Genome Research 2022, 32: 1655-1668. PMID: 36109149, PMCID: PMC9528986, DOI: 10.1101/gr.276578.122.Peer-Reviewed Original ResearchMammalian male reproductionArgonaute 2Distinct nuclear functionsConditional knockoutMale reproductionProtein Argonaute 2Abnormal sperm head morphologyMeiotic chromatinAnimal developmentCytoplasmic roleNuclear functionsMale meiosisNuclear roleMRNA translationAgo2 proteinImportant genesNuclear compartmentMRNA transcriptsBiological relevanceSperm head morphologyHead morphologySpermatogenic cellsWidespread associationChromatinProteinProteomic characterization of post-mortem human brain tissue following ultracentrifugation-based subcellular fractionation
Kandigian SE, Ethier EC, Kitchen RR, Lam TT, Arnold SE, Carlyle BC. Proteomic characterization of post-mortem human brain tissue following ultracentrifugation-based subcellular fractionation. Brain Communications 2022, 4: fcac103. PMID: 35611312, PMCID: PMC9123841, DOI: 10.1093/braincomms/fcac103.Peer-Reviewed Original ResearchProteomic characterizationSubcellular fractionationTissue cell type compositionMultiple cellular organellesPost-mortem human brain tissueMajority of proteinsThousands of proteinsCell type compositionHuman brain tissueSame biological sampleSpatial proteomicsProtein functionProtein localizationOrganellar markersCellular organellesCellular localizationDrug targetsSubcellular levelOrganellesAbundant organellesCentrifugation fractionsProteinCell linesDisease mechanismsMembrane breakdownIdentification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function
Gorenberg EL, Tieze S, Yücel B, Zhao HR, Chou V, Wirak GS, Tomita S, Lam TT, Chandra SS. Identification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function. PLOS Biology 2022, 20: e3001590. PMID: 35358180, PMCID: PMC9004782, DOI: 10.1371/journal.pbio.3001590.Peer-Reviewed Original ResearchConceptsPalmitoyl-protein thioesterase 1Disulfide bond formationNeuronal ceroid lipofuscinosisPosttranslational modificationsRole of PPT1Identification of substratesResin-assisted captureEnzyme palmitoyl-protein thioesterase 1Synaptic adhesion moleculesNeurodegenerative diseasesMature proteinMitochondrial proteinsMolecular dissectionPutative substratesDepalmitoylationKnockout mouse brainFunction mutationsStringent screenMolecular pathwaysSynapse functionDisulfide bondsProteinDevastating neurodegenerative diseaseDisease mechanismsSynaptic functionMycobacterium tuberculosis encodes a YhhN family membrane protein with lysoplasmalogenase activity that protects against toxic host lysolipids
Jurkowitz MS, Azad AK, Monsma PC, Keiser TL, Kanyo J, Lam TT, Bell CE, Schlesinger LS. Mycobacterium tuberculosis encodes a YhhN family membrane protein with lysoplasmalogenase activity that protects against toxic host lysolipids. Journal Of Biological Chemistry 2022, 298: 101849. PMID: 35314194, PMCID: PMC9052158, DOI: 10.1016/j.jbc.2022.101849.Peer-Reviewed Original ResearchConceptsMembrane proteinsIntegral membrane proteinsVinyl ether bondHuman macrophagesPathogen Mycobacterium tuberculosisSn-1 positionSubclass of glycerophospholipidsGrowth advantageHost lipidsProteinFatty aldehydesMycobacterium smegmatisPhospholipase ASn-2 carbonSpheroplastsGlycerol backboneCell densityPlasmalogensCellsMycobacterium tuberculosisMacrophagesGenesOverexpressionLysoplasmenylcholinePLPC
2021
Sex Differences in the Ventral Tegmental Area and Nucleus Accumbens Proteome at Baseline and Following Nicotine Exposure
Lee AM, Mansuri MS, Wilson RS, Lam TT, Nairn AC, Picciotto MR. Sex Differences in the Ventral Tegmental Area and Nucleus Accumbens Proteome at Baseline and Following Nicotine Exposure. Frontiers In Molecular Neuroscience 2021, 14: 657064. PMID: 34335180, PMCID: PMC8317211, DOI: 10.3389/fnmol.2021.657064.Peer-Reviewed Original ResearchVentral tegmental areaC3H/HeJ miceGlial fibrillary acidic proteinChronic nicotine administrationNicotine administrationProtein abundanceProteomeIsobaric labelingNicotine exposureFemale miceTegmental areaHeJ miceNucleus accumbensNicotine addictionProteinSex differencesSample fractionationPathwayFibrillary acidic proteinTandem mass spectrometryNetwork analysisMouse strainsChronic nicotineMesolimbic systemNicotine reward
2020
Differential Protein Expression in Striatal D1- and D2-Dopamine Receptor-Expressing Medium Spiny Neurons
Mansuri MS, Peng G, Wilson RS, Lam TT, Zhao H, Williams KR, Nairn AC. Differential Protein Expression in Striatal D1- and D2-Dopamine Receptor-Expressing Medium Spiny Neurons. Proteomes 2020, 8: 27. PMID: 33066078, PMCID: PMC7709116, DOI: 10.3390/proteomes8040027.Peer-Reviewed Original ResearchFluorescence-activated nuclear sortingTranslating Ribosome Affinity PurificationSpecific neuronal cell typesBiological replicatesNeuronal cell typesCell typesRibosome affinity purificationDifferential protein expressionSpecific cell typesMice/Major cell typesNuclear sortingMass spectrometry analysisProteome analysisAffinity purificationNeuronal cell populationsMedium spiny neuronsProteinProteomeProtein expressionSpectrometry analysisCell populationsAdaptive changesNetwork analysisReproducible workflowsNutrient Composition and Fatty Acid and Protein Profiles of Selected Fish By-Products
Kandyliari A, Mallouchos A, Papandroulakis N, Golla JP, Lam TT, Sakellari A, Karavoltsos S, Vasiliou V, Kapsokefalou M. Nutrient Composition and Fatty Acid and Protein Profiles of Selected Fish By-Products. Foods 2020, 9: 190. PMID: 32075005, PMCID: PMC7074476, DOI: 10.3390/foods9020190.Peer-Reviewed Original ResearchProtein profilesNicotinamide adenine dinucleotide dehydrogenaseSignificant protein sourceSubunit 8Fish speciesAbundant proteinsFatty acidsNutrient compositionSubunit epsilonFishFish samplesProcessing of fishProtein sourceNutritional valueNutritive contentEicosenoic acidValuable sourceAcidAquacultureSpeciesProteinDehydrogenaseGood sourceNutrientsEpsilon
2019
A single phosphoacceptor residue in BGLF3 is essential for transcription of Epstein-Barr virus late genes
Li J, Walsh A, Lam TT, Delecluse HJ, El-Guindy A. A single phosphoacceptor residue in BGLF3 is essential for transcription of Epstein-Barr virus late genes. PLOS Pathogens 2019, 15: e1007980. PMID: 31461506, PMCID: PMC6713331, DOI: 10.1371/journal.ppat.1007980.Peer-Reviewed Original ResearchConceptsPost-translational modificationsLate gene expressionLate genesGene expressionPhosphoacceptor residuesPre-initiation complexPotential phosphorylation sitesViral DNA replicationNew virus particlesEarly gene expressionPhosphorylation sitesVirus particlesDNA replicationTATA boxHerpesvirus proteinsEctopic expressionTrimeric complexLate proteinsLate transcriptsHost cellsEarly proteinsGenesTranscriptionLate kineticsProteinDevelopment of Targeted Mass Spectrometry-Based Approaches for Quantitation of Proteins Enriched in the Postsynaptic Density (PSD)
Wilson RS, Rauniyar N, Sakaue F, Lam TT, Williams KR, Nairn AC. Development of Targeted Mass Spectrometry-Based Approaches for Quantitation of Proteins Enriched in the Postsynaptic Density (PSD). Proteomes 2019, 7: 12. PMID: 30986977, PMCID: PMC6630806, DOI: 10.3390/proteomes7020012.Peer-Reviewed Original ResearchParallel reaction monitoringPostsynaptic densityData-independent acquisition (DIA) approachElectron-dense regionsQuantitation of proteinsBiochemical fractionationMass spectrometry analysisMass spectrometry-based assayProtein abundanceExcitatory glutamatergic synapsesPSD compositionProtein compositionPSD proteinsInternal peptide standardsPSD fractionProteinTargeted Mass SpectrometrySpectrometry analysisGlutamatergic synapsesMass spectrometryPeptide standardsAbundanceNeuropsychiatric disordersCortical brain tissueWide variety
2018
Mapping the Proteome of the Synaptic Cleft through Proximity Labeling Reveals New Cleft Proteins
Cijsouw T, Ramsey AM, Lam TT, Carbone BE, Blanpied TA, Biederer T. Mapping the Proteome of the Synaptic Cleft through Proximity Labeling Reveals New Cleft Proteins. Proteomes 2018, 6: 48. PMID: 30487426, PMCID: PMC6313906, DOI: 10.3390/proteomes6040048.Peer-Reviewed Original ResearchProximity labelingLabel-free quantitation mass spectrometryReceptor-type tyrosine-protein phosphatase zetaProximity labeling approachCell-cell contactSynaptic cleftPost-synaptic specializationsProteomic contentSynapse heterogeneitySynCAM 1Confocal microcopySurface proteinsCell surfaceProteomeSuper-resolution imagingCultured cortical neuronsMammalian brainLabeling approachMolecular compositionReporterProteinCortical neuronsFunctional organizationExcitatory synapsesDiverse set
2017
The repeat region of cortactin is intrinsically disordered in solution
Li X, Tao Y, Murphy JW, Scherer AN, Lam TT, Marshall AG, Koleske AJ, Boggon TJ. The repeat region of cortactin is intrinsically disordered in solution. Scientific Reports 2017, 7: 16696. PMID: 29196701, PMCID: PMC5711941, DOI: 10.1038/s41598-017-16959-1.Peer-Reviewed Original ResearchConceptsCortactin repeatsRepeat regionActin filamentsHydrogen-deuterium exchange mass spectrometryAdjacent helical regionsMulti-domain proteinsExchange mass spectrometryExtensive biophysical analysisCircular dichroismHydrophobic core regionSmall-angle X-ray scatteringBiophysical analysisHelical regionCortactinRepeatsSimilar copiesUnfolded peptidesProteinMotifSize exclusion chromatographyMass spectrometryFilamentsExclusion chromatographyX-ray scatteringRegionA multiregional proteomic survey of the postnatal human brain
Carlyle BC, Kitchen RR, Kanyo JE, Voss EZ, Pletikos M, Sousa AMM, Lam TT, Gerstein MB, Sestan N, Nairn AC. A multiregional proteomic survey of the postnatal human brain. Nature Neuroscience 2017, 20: 1787-1795. PMID: 29184206, PMCID: PMC5894337, DOI: 10.1038/s41593-017-0011-2.Peer-Reviewed Original ResearchConceptsProteomic surveyResident plasma membrane proteinsPostnatal human brainProtein dataPlasma membrane proteinsProtein abundance differencesQuantitative tandem mass spectrometryPost-translational eventsWhole transcriptome sequencingRNA expression dataMembrane proteinsFunctional variationExpression dataAbundance differencesBrain regionsTandem mass spectrometryHuman brainSimilar cortical regionsMass spectrometryEarly infancyRNACortical regionsSequencingProteinAbundance
2016
Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex
McClure-Begley TD, Esterlis I, Stone KL, Lam TT, Grady SR, Colangelo CM, Lindstrom JM, Marks MJ, Picciotto MR. Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex. ENeuro 2016, 3: eneuro.0166-16.2016. PMID: 27559543, PMCID: PMC4985585, DOI: 10.1523/eneuro.0166-16.2016.Peer-Reviewed Original ResearchConceptsPutative interacting proteinsQuantitative proteomic assessmentProtein-protein interactionsTemporal cortex tissueChaperone familyMood disordersInteracting proteinProtein complexesPresynaptic neurotransmitter releaseNovel etiological mechanismsNicotine exposureProteomic assessmentProteomeNicotinic acetylcholine receptorsMouse cortexProteinHigh-affinity nAChRsΒ2 subunitCortex of miceMaintenance of smokingNew treatment targetsResult of smokingNeurotransmitter releaseAcetylcholine receptorsPrimary functionSILAC based protein profiling data of MKK3 knockout mouse embryonic fibroblasts
Srivastava A, Shinn AS, Lam TT, Lee PJ, Mannam P. SILAC based protein profiling data of MKK3 knockout mouse embryonic fibroblasts. Data In Brief 2016, 7: 418-422. PMID: 26977448, PMCID: PMC4782019, DOI: 10.1016/j.dib.2016.02.034.Peer-Reviewed Original ResearchMouse embryonic fibroblastsYale Protein Expression DatabaseIngenuity Pathway AnalysisEmbryonic fibroblastsKnockout mouse embryonic fibroblastsProtein Expression DatabaseWT mouse embryonic fibroblastsQuantitative mass spectrometryWhole cell lysatesTotal proteomeIntegrated DiscoveryMAP kinasePathway analysisAltered pathwaysCell lysatesMass spectrometry dataSILACPhosphopeptide enrichmentProtein levelsExpression databaseProteinSpectrometry dataPathwayFibroblastsMass spectrometry
2015
Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation
Henderson MX, Wirak GS, Zhang YQ, Dai F, Ginsberg SD, Dolzhanskaya N, Staropoli JF, Nijssen PC, Lam TT, Roth AF, Davis NG, Dawson G, Velinov M, Chandra SS. Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation. Acta Neuropathologica 2015, 131: 621-637. PMID: 26659577, PMCID: PMC4791186, DOI: 10.1007/s00401-015-1512-2.Peer-Reviewed Original ResearchConceptsNeuronal ceroid lipofuscinosesProtein palmitoylationDisease pathwaysPalmitoyl-protein thioesterase 1Forms of NCLEnzyme palmitoyl-protein thioesterase 1Disease-associated proteinsCommon disease pathwaysNCL genesQuantitative proteomicsCSPα mutationsSpecific enzymatic activityCSPαFunctional linkNeuronal ceroid lipofuscinosisGlobal changePPT1Synaptic proteinsEnzymatic activityCeroid lipofuscinosesPalmitoylationGenesCeroid lipofuscinosisNeurodegenerative disordersProtein
2012
Interaction of the Histone mRNA Hairpin with Stem–Loop Binding Protein (SLBP) and Regulation of the SLBP–RNA Complex by Phosphorylation and Proline Isomerization
Zhang M, Lam TT, Tonelli M, Marzluff WF, Thapar R. Interaction of the Histone mRNA Hairpin with Stem–Loop Binding Protein (SLBP) and Regulation of the SLBP–RNA Complex by Phosphorylation and Proline Isomerization. Biochemistry 2012, 51: 3215-3231. PMID: 22439849, PMCID: PMC3328597, DOI: 10.1021/bi2018255.Peer-Reviewed Original ResearchConceptsStem-loop binding proteinStem-loop structureHistone mRNAProline isomerizationThreonine phosphorylationEnd formationC base pairsReplication-dependent histone mRNAsBase pairsBinding proteinPossible structural roleAdjacent prolineHistone proteinsRibonucleoprotein complexesHelix motifMRNA hairpinsMRNA complexesUntranslated regionStructural roleFirst binding sitePhosphorylationProteinComplex dissociationCritical hingeMRNA
2009
Diversification of a Salmonella Virulence Protein Function by Ubiquitin-Dependent Differential Localization
Patel JC, Hueffer K, Lam TT, Galán JE. Diversification of a Salmonella Virulence Protein Function by Ubiquitin-Dependent Differential Localization. Cell 2009, 137: 283-294. PMID: 19379694, PMCID: PMC2673707, DOI: 10.1016/j.cell.2009.01.056.Peer-Reviewed Original ResearchConceptsEffector proteinsCellular functionsType III secretion systemBacterial effector proteinsUbiquitin-dependent mannerDifferent cellular compartmentsHost cellular machinerySame enzymatic activityVesicular traffickingCellular machineryProtein functionSecretion systemCellular compartmentsBacterial internalizationFunctional repertoirePlasma membraneRegulated mannerAkt activationHost cellsDifferential localizationBacterial replicationVirulence factorsEnzymatic activityBacterial pathogensProtein