2024
An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms
Hart T, Sonnert N, Tang X, Chaurasia R, Allen P, Hunt J, Read C, Johnson E, Arora G, Dai Y, Cui Y, Chuang Y, Yu Q, Rahman M, Mendes M, Rolandelli A, Singh P, Tripathi A, Ben Mamoun C, Caimano M, Radolf J, Lin Y, Fingerle V, Margos G, Pal U, Johnson R, Pedra J, Azad A, Salje J, Dimopoulos G, Vinetz J, Carlyon J, Palm N, Fikrig E, Ring A. An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms. Cell 2024, 187: 4113-4127.e13. PMID: 38876107, PMCID: PMC11959484, DOI: 10.1016/j.cell.2024.05.023.Peer-Reviewed Original ResearchCell invasionHost-microbe interactionsArthropod-borne pathogensHost sensingMicrobe interactionsTranscriptional regulationLyme disease spirocheteMicrobial interactionsExtracellular proteinsMicrobial pathogenesisEpidermal growth factorTissue colonizationEnvironmental cuesBacterial selectivityIntracellular pathogensPutative interactionsNext-generation therapeuticsPathogensFunctional investigationsInteractomeVector-borne diseasesImmune evasionPathogenic mechanismsStrainUnmet medical needBifunctional Molecules That Induce Both Targeted Degradation and Transcytosis of Extracellular Proteins in Brain Cells
Howell R, Wang S, Khambete M, McDonald D, Spiegel D. Bifunctional Molecules That Induce Both Targeted Degradation and Transcytosis of Extracellular Proteins in Brain Cells. Journal Of The American Chemical Society 2024, 146: 16404-16411. PMID: 38855935, DOI: 10.1021/jacs.3c13320.Peer-Reviewed Original ResearchLow-density lipoprotein receptor-related protein 1Targeted Protein DegradationTarget proteinsClathrin-mediated mechanismLipoprotein receptor-related protein 1Chloroalkane ligandTranscytosis of proteinsExtracellular proteinsPeptide motifsLysosomal localizationTargeted degradationHaloTag proteinCovalent taggingProtein degradationLysosomal proteolysisBlood-brain barrierProteinDegradable proteinCentral nervous systemProtein 1Bifunctional small moleculesEffective therapeutic strategyPrimary receptorTranscytosisStreptavidin
2021
Bifunctional small molecules that mediate the degradation of extracellular proteins
Caianiello DF, Zhang M, Ray JD, Howell RA, Swartzel JC, Branham EMJ, Chirkin E, Sabbasani VR, Gong AZ, McDonald DM, Muthusamy V, Spiegel DA. Bifunctional small molecules that mediate the degradation of extracellular proteins. Nature Chemical Biology 2021, 17: 947-953. PMID: 34413525, DOI: 10.1038/s41589-021-00851-1.Peer-Reviewed Original ResearchConceptsExtracellular proteinsTarget proteinsUbiquitin-proteasome systemBifunctional small moleculesSynthetic moleculesProtein degradationIntracellular proteinsProinflammatory cytokine proteinProteinLysosomal proteasesTernary complexSmall moleculesPromising therapeutic strategyCytokine proteinsTherapeutic strategiesMoleculesDegradationProteaseDisease treatmentExperimental evidence
2018
Engineering tyrosine residues into hemoglobin enhances heme reduction, decreases oxidative stress and increases vascular retention of a hemoglobin based blood substitute
Cooper C, Silkstone G, Simons M, Rajagopal B, Syrett N, Shaik T, Gretton S, Welbourn E, Bülow L, Eriksson N, Ronda L, Mozzarelli A, Eke A, Mathe D, Reeder B. Engineering tyrosine residues into hemoglobin enhances heme reduction, decreases oxidative stress and increases vascular retention of a hemoglobin based blood substitute. Free Radical Biology And Medicine 2018, 134: 106-118. PMID: 30594736, PMCID: PMC6597946, DOI: 10.1016/j.freeradbiomed.2018.12.030.Peer-Reviewed Original ResearchConceptsTyrosine residuesΒ-subunitSingle tyrosine mutationsFerryl heme speciesOxidative stressExtracellular proteinsTyrosine mutationWild typePromising mutantsHEK cellsProtein surfaceHeme speciesMutationsMembrane damageRedox-active tyrosine residueHeme reductionOxidative toxicityFerryl speciesFerric HbSubunitsHb additionHeme lossSpeciesProteinFerric formExtracellular anti-angiogenic proteins augment an endosomal protein trafficking pathway to reach mitochondria and execute apoptosis in HUVECs
Chen M, Qiu T, Wu J, Yang Y, Wright GD, Wu M, Ge R. Extracellular anti-angiogenic proteins augment an endosomal protein trafficking pathway to reach mitochondria and execute apoptosis in HUVECs. Cell Death & Differentiation 2018, 25: 1905-1920. PMID: 29523874, PMCID: PMC6219483, DOI: 10.1038/s41418-018-0092-9.Peer-Reviewed Original ResearchMeSH KeywordsAngiostatinsApoptosisCell MembraneEndocytosisEndoplasmic Reticulum Chaperone BiPEndosomesFibronectinsFluorescence Recovery After PhotobleachingHeat-Shock ProteinsHuman Umbilical Vein Endothelial CellsHumansMicroscopy, FluorescenceMitochondriaNeovascularization, PhysiologicPhosphoproteinsProtein TransportRecombinant ProteinsRNA InterferenceRNA, Small InterferingSodium-Hydrogen ExchangersSynaptosomal-Associated Protein 25ThrombospondinsConceptsLate endosomesEndosomal proteinExtracellular proteinsT-SNARE proteinsCytosolic scaffold proteinsTotal internal reflection fluorescent microscopyPro-apoptotic functionFluorescent microscopyRegulatory factor 1Recycling endosomesRNAi knockdownCargo degradationScaffold proteinSuper-resolution fluorescent microscopyMitochondrial traffickingCell fractionationPlasma membraneIsthminProximity ligationMitochondriaProtein 25ProteinBiochemical analysisAnti-angiogenic proteinFactor 1
2013
Angiopoietin-2 Secretion by Endothelial Cell Exosomes REGULATION BY THE PHOSPHATIDYLINOSITOL 3-KINASE (PI3K)/Akt/ENDOTHELIAL NITRIC OXIDE SYNTHASE (eNOS) AND SYNDECAN-4/SYNTENIN PATHWAYS*
Ju R, Zhuang ZW, Zhang J, Lanahan AA, Kyriakides T, Sessa WC, Simons M. Angiopoietin-2 Secretion by Endothelial Cell Exosomes REGULATION BY THE PHOSPHATIDYLINOSITOL 3-KINASE (PI3K)/Akt/ENDOTHELIAL NITRIC OXIDE SYNTHASE (eNOS) AND SYNDECAN-4/SYNTENIN PATHWAYS*. Journal Of Biological Chemistry 2013, 289: 510-519. PMID: 24235146, PMCID: PMC3879572, DOI: 10.1074/jbc.m113.506899.Peer-Reviewed Original ResearchConceptsPI3K/Akt/endothelial nitric oxide synthaseAkt/endothelial nitric oxide synthaseAkt1 null miceCritical signaling pathwaysMode of secretionEndothelial nitric oxide synthaseExtracellular proteinsSignaling pathwaysSyndecan-4Angiopoietin/Tie2Novel mechanismVascular defectsNitric oxide synthaseAngiopoietin-2 secretionNull miceTie2 receptorPathwayPrincipal ligandEndothelial cellsSynthaseVascular integrityRegulationOxide synthaseVascular growthImportant role
2011
FACS purification of immunolabeled cell types from adult rat brain
Guez-Barber D, Fanous S, Harvey BK, Zhang Y, Lehrmann E, Becker KG, Picciotto MR, Hope BT. FACS purification of immunolabeled cell types from adult rat brain. Journal Of Neuroscience Methods 2011, 203: 10-18. PMID: 21911005, PMCID: PMC3221768, DOI: 10.1016/j.jneumeth.2011.08.045.Peer-Reviewed Original ResearchConceptsFluorescence-activated cell sortingCell typesPromoter-driven reporter geneBrain tissueExtracellular proteinsFACS procedureReporter geneFACS purificationRat brainReal-time PCRMolecular analysisSorted cellsCell sortingAdult rat brainTime PCRIntact cell bodiesTransgenic miceMolecular alterationsNeuN antibodyQuantitative assayCell bodiesAvailable antibodiesBrainTissueGenes
2008
Heterozygous expression of myocilin glaucoma mutants increases secretion of the mutant forms and reduces extracellular processed myocilin.
Aroca-Aguilar JD, Sánchez-Sánchez F, Martínez-Redondo F, Coca-Prados M, Escribano J. Heterozygous expression of myocilin glaucoma mutants increases secretion of the mutant forms and reduces extracellular processed myocilin. Molecular Vision 2008, 14: 2097-108. PMID: 19023451, PMCID: PMC2585175.Peer-Reviewed Original ResearchConceptsWild-type myocilinWild-type proteinMyocilin mutantsMutant myocilinMutant formsProteolytic processingMissense mutant formsHEK 293T cellsMyocilin geneMutant proteinsSecretory pathwayUnidentified functionExtracellular proteinsMutantsEndoproteolytic processingRecombinant mutantsMyocilin secretionCellular fractionsHeterozygous expressionMyocilinProteinUnknown mechanismExtracellular amountSDS-PAGEHeterozygous state
2007
Syndecans
Tkachenko E, Rhodes J, Simons M. Syndecans. 2007, 396-402. DOI: 10.1017/cbo9780511546198.045.Peer-Reviewed Original ResearchSyndecan familyCore proteinExtracellular domainMembrane-anchored proteinsHeparan sulfateLarger heparan sulfateExtracellular matrix proteinsDifferent core proteinsCell surface receptorsSignaling inputsTransmembrane proteinSuch proteinsExtracellular proteinsDistinct functionsMatrix proteinsSyndecansProtein coreWide expressionSurface receptorsProteinGlycosaminoglycan chainsAttachment sitesRepeating disaccharide unitCS chainsTransmembrane
2000
The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein
Pusch C, Zeitz C, Brandau O, Pesch K, Achatz H, Feil S, Scharfe C, Maurer J, Jacobi F, Pinckers A, Andreasson S, Hardcastle A, Wissinger B, Berger W, Meindl A. The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein. Nature Genetics 2000, 26: 324-327. PMID: 11062472, DOI: 10.1038/81627.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceBrainChromosome MappingDNA Mutational AnalysisDNA, ComplementaryElectroretinographyEye ProteinsFemaleGene Expression ProfilingGenesGenetic HeterogeneityGenetic MarkersGlycosylphosphatidylinositolsHumansKidneyLeucineMaleModels, MolecularMolecular Sequence DataMultigene FamilyMuscle ProteinsMusclesNerve Tissue ProteinsNight BlindnessOrgan SpecificityPedigreeProtein ConformationProteoglycansRepetitive Sequences, Amino AcidRetinaReverse Transcriptase Polymerase Chain ReactionSequence DeletionSequence Homology, Amino AcidTestisX ChromosomeConceptsLeucine-rich repeatsLeucine-rich repeat proteinFuture functional analysisProtein-protein interactionsCell-cell contactProximal short armCongenital stationary night blindnessGenetic mappingNew genesX chromosome2Repeat proteinsExtracellular proteinsLinkage intervalFunctional analysisStationary night blindnessDifferent lociShort armCell adhesionAmino acidsGenesCSNB1 locusProteinDifferent mutationsLociMutation analysis
1998
Mice That Lack Thrombospondin 2 Display Connective Tissue Abnormalities That Are Associated with Disordered Collagen Fibrillogenesis, an Increased Vascular Density, and a Bleeding Diathesis
Kyriakides T, Zhu Y, Smith L, Bain S, Yang Z, Lin M, Danielson K, Iozzo R, LaMarca M, McKinney C, Ginns E, Bornstein P. Mice That Lack Thrombospondin 2 Display Connective Tissue Abnormalities That Are Associated with Disordered Collagen Fibrillogenesis, an Increased Vascular Density, and a Bleeding Diathesis. Journal Of Cell Biology 1998, 140: 419-430. PMID: 9442117, PMCID: PMC2132586, DOI: 10.1083/jcb.140.2.419.Peer-Reviewed Original ResearchConceptsTSP2-null miceEmbryonic stem cellsCollagen fibrillogenesisGenetic disorder resultsCell surface propertiesHomologous recombinationExtracellular proteinsMutant animalsBlastocyst injectionAppropriate breedingStructural roleMendelian frequencyMouse tissuesMesenchymal cellsStem cellsUnusual phenotypeCell functionMutant miceThrombospondin-2TSP2Von Willebrand factorSkin fibroblastsConnective tissue abnormalitiesLarge fibrilsWillebrand factor
1997
Neuronal and Non-Neuronal Collapsin-1 Binding Sites in Developing Chick Are Distinct from Other Semaphorin Binding Sites
Takahashi T, Nakamura F, Strittmatter S. Neuronal and Non-Neuronal Collapsin-1 Binding Sites in Developing Chick Are Distinct from Other Semaphorin Binding Sites. Journal Of Neuroscience 1997, 17: 9183-9193. PMID: 9364065, PMCID: PMC6573609, DOI: 10.1523/jneurosci.17-23-09183.1997.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAvian ProteinsAxonsBinding SitesCells, CulturedCentral Nervous SystemChick EmbryoDNA, ComplementaryFetal ProteinsGanglia, SpinalGlycoproteinsLungMembrane ProteinsMesodermMiceMotor NeuronsMultigene FamilyNerve Growth FactorsNerve Tissue ProteinsNeuronsNeurotrophin 3Organ SpecificityRatsRats, Sprague-DawleyReceptors, Cell SurfaceRecombinant Fusion ProteinsSemaphorin-3AConceptsFusion proteinBinding sitesGrowth conesDRG neuronsNon-neuronal tissuesExtracellular proteinsF fusion proteinSemaphorin familyDRG growth conesProteinLow nanomolar affinityMajor blood vesselsLigand familyBrainstem neuronsSympathetic neuronsNanomolar affinityNervous systemAxonal pathsBiological activityBlood vesselsNeuronsFamilySitesMesenchymeSemaphorins
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