2022
Structural basis for inhibition of the Cation-chloride cotransporter NKCC1 by the diuretic drug bumetanide
Zhao Y, Roy K, Vidossich P, Cancedda L, De Vivo M, Forbush B, Cao E. Structural basis for inhibition of the Cation-chloride cotransporter NKCC1 by the diuretic drug bumetanide. Nature Communications 2022, 13: 2747. PMID: 35585053, PMCID: PMC9117670, DOI: 10.1038/s41467-022-30407-3.Peer-Reviewed Original ResearchConceptsTranslocation pathwayElectron cryo-microscopy structureC-terminal domainIon translocation pathwayCation-chloride cotransporters NKCC1Transmembrane domainCotransporter NKCC1C-terminal domain interactionsStructural basisDomain interactionsRenal salt reabsorptionDomain associationConformational changesFunctional studiesIon translocationElectroneutral symportCell membraneNKCC1PathwayNKCC2DomainSalt reabsorptionTransmembraneTranslocationTransporters
2021
The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2
Zhang S, Zhou J, Zhang Y, Liu T, Friedel P, Zhuo W, Somasekharan S, Roy K, Zhang L, Liu Y, Meng X, Deng H, Zeng W, Li G, Forbush B, Yang M. The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2. Communications Biology 2021, 4: 226. PMID: 33597714, PMCID: PMC7889885, DOI: 10.1038/s42003-021-01750-w.Peer-Reviewed Original ResearchConceptsCryo-electron microscopy structureHuman NKCC1Microscopy structureEssential residuesFunctional characterizationKCC transportersPlasma membraneStructural basisTransepithelial saltTransport activityMechanistic understandingTransportersStructural studiesCritical roleCotransporter NKCC1Computational analysisIon transportWater transportNeuronal excitabilityNKCC1PhosphorylationCell volumeNKCCKCC2Residues
2019
Lipid Modifications in Cilia Biology
Roy K, Marin EP. Lipid Modifications in Cilia Biology. Journal Of Clinical Medicine 2019, 8: 921. PMID: 31252577, PMCID: PMC6678300, DOI: 10.3390/jcm8070921.BooksLipid modificationCiliary proteinsCiliary protein traffickingSpecific protein poolsDifferent lipid modificationsCilia biologyProtein traffickingProtein stabilitySignaling cascadesTransporter proteinsProtein poolProteinVariety of rolesCiliaTraffickingFinal localizationCellular structureDistinctive roleBiologyRoleAbundanceModificationRegulationPathwayCascadeReceptor tyrosine kinases (RTKs) consociate in regulatory clusters in Alzheimer’s disease and type 2 diabetes
Majumder P, Roy K, Bagh S, Mukhopadhyay D. Receptor tyrosine kinases (RTKs) consociate in regulatory clusters in Alzheimer’s disease and type 2 diabetes. Molecular And Cellular Biochemistry 2019, 459: 171-182. PMID: 31154588, DOI: 10.1007/s11010-019-03560-5.Peer-Reviewed Original ResearchConceptsType 2 diabetesAlzheimer's diseaseReceptor tyrosine kinasesPost-mortem Alzheimer's diseaseFuture therapeutic developmentInsulin resistanceDisease typeActivity statusDiseaseCommon hallmarkTherapeutic developmentDefinitive roleDiabetesOne-thirdTyrosine kinaseCell modelSimilar regulatory mechanismsT2D.Regulatory mechanisms
2018
Polycystin-1, the product of the polycystic kidney disease gene PKD1, is post-translationally modified by palmitoylation
Roy K, Marin EP. Polycystin-1, the product of the polycystic kidney disease gene PKD1, is post-translationally modified by palmitoylation. Molecular Biology Reports 2018, 45: 1515-1521. PMID: 30073588, DOI: 10.1007/s11033-018-4224-6.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseProteins polycystin-1End-stage renal diseasePossible pharmacologic targetsStage renal diseasePossible modifiable factorsRate of progressionDominant polycystic kidney diseaseExpression levelsPolycystic kidney diseaseRenal diseaseKidney diseaseModifiable factorsCommon causePharmacologic targetPolycystin-1Carboxyl-terminal fragmentKidney cystsPC1 expressionPotential causesDiseaseDistinct mutationsPost-translational modificationsMultiple complementary approachesGenes PKD1
2017
Palmitoylation of the ciliary GTPase ARL13b is necessary for its stability and its role in cilia formation
Roy K, Jerman S, Jozsef L, McNamara T, Onyekaba G, Sun Z, Marin EP. Palmitoylation of the ciliary GTPase ARL13b is necessary for its stability and its role in cilia formation. Journal Of Biological Chemistry 2017, 292: 17703-17717. PMID: 28848045, PMCID: PMC5663873, DOI: 10.1074/jbc.m117.792937.Peer-Reviewed Original ResearchConceptsPost-translational attachmentMost mammalian cellsCiliary GTPase Arl13bCilia localizationProtein palmitoylationCiliary proteinsCilia proteinsProtein localizationCilia formationMammalian cellsCilia functionPalmitoylationPrimary ciliaPlasma membraneCilia resorptionArl13bFunctional importanceMyristoylationCiliaCritical roleProteinMouse kidneyLocalizationDepalmitoylationCellsCellular levels of Grb2 and cytoskeleton stability are correlated in a neurodegenerative scenario
Majumder P, Roy K, Singh BK, Jana NR, Mukhopadhyay D. Cellular levels of Grb2 and cytoskeleton stability are correlated in a neurodegenerative scenario. Disease Models & Mechanisms 2017, 10: 655-669. PMID: 28360125, PMCID: PMC5451165, DOI: 10.1242/dmm.027748.Peer-Reviewed Original ResearchConceptsAD-like conditionsDisease manifestCytoskeletal architecturePak1 proteinCytoskeleton stabilityAD mouse brainCytoskeletal proteinsGrb2 overexpressionGrb2Β-amyloid oligomersPotential new strategyCellular levelNeuronal lossAD patientsPreventive roleCytoskeletonProteinMouse brainBrain tissueExtracellular accumulationPotent inducerMolecular featuresUnique roleDomain levelCytoskeletal
2014
Interaction of Grb2 SH3 domain with UVRAG in an Alzheimer’s disease–like scenario
Roy K, Chakrabarti O, Mukhopadhyay D. Interaction of Grb2 SH3 domain with UVRAG in an Alzheimer’s disease–like scenario. Biochemistry And Cell Biology 2014, 92: 219-225. PMID: 24882360, DOI: 10.1139/bcb-2014-0001.Peer-Reviewed Original ResearchConceptsSrc homology 3SH3 domainGrowth factor receptor-bound protein 2Receptor-bound protein 2C-terminal SH3 domainIntracellular domain interactionsN-terminal SH3 domainRole of Grb2Autophagic maturationHomology 3Actin remodelingAdaptor proteinCellular compartmentalizationGrb2Cell line modelsDomain interactionsGene proteinProtein 2ProteinAutophagosomesExcess conditionsVesiclesDomainCompartmentalizationMotif
2013
Differential Expression of Neuroblastoma Cellular Proteome due to AICD Overexpression
Chakrabarti A, Roy K, Mukhopadhyay D. Differential Expression of Neuroblastoma Cellular Proteome due to AICD Overexpression. Journal Of Alzheimer's Disease 2013, 38: 845-855. PMID: 24081375, DOI: 10.3233/jad-130695.Peer-Reviewed Original ResearchConceptsAmyloid-β protein precursor intracellular domainCell linesProteomic expression patternsDifferent functional classesCellular proteomeCytoskeletal dynamicsProtein foldingIntracellular domainExpression patternsBiological processesBiological pathwaysMALDI-MS identificationNormal proteomeDifferential expressionSHSY5Y cell lineNeuroblastoma cell linesKey playersProteomeAlzheimer's diseaseProtein overloadArtifactual consequenceProteinAD-like conditionsAD phenotypePathophysiological effectsGrowth Factor Receptor-Bound Protein 2 Promotes Autophagic Removal of Amyloid-β Protein Precursor Intracellular Domain Overload in Neuronal Cells
Roy K, Raychaudhuri M, Chakrabarti O, Mukhopadhyay D. Growth Factor Receptor-Bound Protein 2 Promotes Autophagic Removal of Amyloid-β Protein Precursor Intracellular Domain Overload in Neuronal Cells. Journal Of Alzheimer's Disease 2013, 38: 881-895. PMID: 24100123, DOI: 10.3233/jad-130929.Peer-Reviewed Original ResearchConceptsAmyloid-β protein precursor intracellular domainRole of Grb2Dynamin-independent mannerTypes of vesiclesAutophagic removalApoptosis pointsGrowth factor receptorIntracellular domainVesicle accumulationCaspase activityDisease brainNeuronal cellsAD cell modelGrb2Independent mannerFactor receptorVesiclesAutophagosomesExcess conditionsAlzheimer's disease brainProtein overloadStudy unravelsCell modelCytotoxic effectsCells
2012
The N-Terminal SH3 Domain of Grb2 is Required for Endosomal Localization of AβPP
Raychaudhuri M, Roy K, Das S, Mukhopadhyay D. The N-Terminal SH3 Domain of Grb2 is Required for Endosomal Localization of AβPP. Journal Of Alzheimer's Disease 2012, 32: 479-493. PMID: 22785391, DOI: 10.3233/jad-2012-120388.Peer-Reviewed Original ResearchConceptsN-SH3 domainSH3 domainLate endosomesC-terminal SH3 domainC-SH3 domainN-terminal SH3 domainTerminal SH3 domainAmyloid-β protein precursorSH2 domainEndosomal localizationEarly endosomesVesicular localizationMolecular basisGrb2Mutational analysisTrafficking routesExosomal releaseProtein precursorExosomal vesiclesSmall punctaEndosomesTraffic impairmentEndogenous levelsVesiclesMixed population