2024
Cellular Prion Protein Conformational Shift after Liquid–Liquid Phase Separation Regulated by a Polymeric Antagonist and Mutations
Liu Y, Tuttle M, Kostylev M, Roseman G, Zilm K, Strittmatter S. Cellular Prion Protein Conformational Shift after Liquid–Liquid Phase Separation Regulated by a Polymeric Antagonist and Mutations. Journal Of The American Chemical Society 2024, 146: 27903-27914. PMID: 39326869, PMCID: PMC11469297, DOI: 10.1021/jacs.4c10590.Peer-Reviewed Original ResearchConceptsLiquid-liquid phase separationCellular prion proteinAssociated with neurodegenerative diseasesAmyloid-bMaturation processDisordered proteinsPrion proteinConformational shiftProtein conformationConformational changesNeurodegenerative diseasesInduction conditionsConformational statesProteinPrPMutationsPhase separationSaturating concentrationsMolecular motionSolid-like stateMaturationDisease-related cognitive deficitsNeurodegenerationInductionAlzheimer
2022
An unexpected protein aggregate in diseased and ageing brains
Takahashi H, Strittmatter SM. An unexpected protein aggregate in diseased and ageing brains. Nature 2022, 605: 227-228. PMID: 35379977, DOI: 10.1038/d41586-022-00873-2.Peer-Reviewed Original Research
2021
Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells
Franjic D, Skarica M, Ma S, Arellano JI, Tebbenkamp ATN, Choi J, Xu C, Li Q, Morozov YM, Andrijevic D, Vrselja Z, Spajic A, Santpere G, Li M, Zhang S, Liu Y, Spurrier J, Zhang L, Gudelj I, Rapan L, Takahashi H, Huttner A, Fan R, Strittmatter SM, Sousa AMM, Rakic P, Sestan N. Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells. Neuron 2021, 110: 452-469.e14. PMID: 34798047, PMCID: PMC8813897, DOI: 10.1016/j.neuron.2021.10.036.Peer-Reviewed Original ResearchConceptsDisease-related proteinsCellular diversityCross-species analysisSingle-nucleus transcriptomesLipid droplet proteinsSpecies-specific propertiesImmature neuron populationTranscriptomic taxonomyAlzheimer's disease-related proteinsEndoplasmic reticulumCell typesHuman neuronsSpecies differencesHistologic signatureNeurogenic capabilityProteinExcitatory neuronsDiversityAdult miceGranule cellsAlzheimer's diseaseNeuron populationsCognitive functionEntorhinal cellsAdult humans
2019
A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration
Sekine Y, Lindborg JA, Strittmatter SM. A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration. Journal Of Biological Chemistry 2019, 295: 2175-2183. PMID: 31748413, PMCID: PMC7039549, DOI: 10.1074/jbc.ra119.009896.Peer-Reviewed Original ResearchConceptsMembrane-associated proteinsRecombinant protein expressionMatrix-associated proteinOligodendrocyte plasma membraneProteolytic C-terminal fragmentsRegeneration assaysC-terminal fragmentPlasma membraneNeurite outgrowth inhibitor NogoAxonal regenerationExosomal releaseDiffusible inhibitorC-terminalSiRNA knockdownCleavage siteCultured cellsLong fragmentPrimary cortical neuron culturesCentral nervous system traumaExosomesEnzyme inhibitor treatmentExosomal fractionSpinal cord crush injuryCerebral cortex neuronsProtein
2018
Liquid and Hydrogel Phases of PrPC Linked to Conformation Shifts and Triggered by Alzheimer’s Amyloid-β Oligomers
Kostylev MA, Tuttle MD, Lee S, Klein LE, Takahashi H, Cox TO, Gunther EC, Zilm KW, Strittmatter SM. Liquid and Hydrogel Phases of PrPC Linked to Conformation Shifts and Triggered by Alzheimer’s Amyloid-β Oligomers. Molecular Cell 2018, 72: 426-443.e12. PMID: 30401430, PMCID: PMC6226277, DOI: 10.1016/j.molcel.2018.10.009.Peer-Reviewed Original ResearchConceptsAmino-terminal GlyCellular prion proteinProtein phase separationAmyloid-β OligomersPlasma membraneMembraneless organellesAla residuesRecombinant PrPPrion proteinCell surfaceConformation shiftConformational transitionHelical conformationAβ speciesPrPSupSpongiform degenerationEndogenous AβOsOrganellesPrPCSuch domainsSpeciesDomainProteinAβOs
2016
Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity
Smith LM, Strittmatter SM. Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity. Cold Spring Harbor Perspectives In Medicine 2016, 7: a024075. PMID: 27940601, PMCID: PMC5411685, DOI: 10.1101/cshperspect.a024075.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAβ oligomersSoluble Aβ oligomersFibrillary amyloidNeuronal impairmentSynaptic dysfunctionAD pathogenesisSynaptic toxicityAmyloid-β OligomersCellular prion proteinNeuronal cascadesFurther studiesCell surface proteinsDiseaseAβPrion proteinOligomer toxicityToxicityDysfunctionMolecular basisPathogenesisDementiaProteinPlaquesImpairmentInhibiting poly(ADP-ribosylation) improves axon regeneration
Byrne AB, McWhirter RD, Sekine Y, Strittmatter SM, Miller DM, Hammarlund M. Inhibiting poly(ADP-ribosylation) improves axon regeneration. ELife 2016, 5: e12734. PMID: 27697151, PMCID: PMC5050021, DOI: 10.7554/elife.12734.Peer-Reviewed Original ResearchConceptsNovel intrinsic regulatorAxon regenerationDLK functionChemical inhibitionIntrinsic regulatorRegeneration pathwayPARG expressionIntrinsic regenerative potentialDLK signalingCritical functionsPARGRegenerative potentialPARP inhibitorsProteinPARPMammalian cortical neuronsRegenerationMotor neuronsGABA neuronsPolymeraseCortical neuronsSignalingRegulatorSpeciesNeurons
2015
Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease
Haas LT, Salazar SV, Kostylev MA, Um JW, Kaufman AC, Strittmatter SM. Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease. Brain 2015, 139: 526-546. PMID: 26667279, PMCID: PMC4840505, DOI: 10.1093/brain/awv356.Peer-Reviewed Original ResearchConceptsCellular prion proteinDisease-related phenotypesPrion proteinMetabotropic glutamate receptor 5Glutamate receptor 5Protein tyrosine kinase 2 betaCalmodulin-dependent protein kinase IICalcium/calmodulin-dependent protein kinase IIProtein kinase IIReceptor 5Protein associatesGenetic interactionsObligate complexesGenetic couplingDisease pathogenesisDisease pathologyKinase IIIntracellular proteinsAlzheimer's disease-related phenotypesSingle heterozygotesProteinBiochemical evidenceProtein mediatorsDisease-modifying interventionsTransgenic model mice
2013
Metabotropic Glutamate Receptor 5 Is a Coreceptor for Alzheimer Aβ Oligomer Bound to Cellular Prion Protein
Um J, Kaufman A, Kostylev M, Heiss J, Stagi M, Takahashi H, Kerrisk M, Vortmeyer A, Wisniewski T, Koleske A, Gunther E, Nygaard H, Strittmatter S. Metabotropic Glutamate Receptor 5 Is a Coreceptor for Alzheimer Aβ Oligomer Bound to Cellular Prion Protein. Neuron 2013, 80: 531. DOI: 10.1016/j.neuron.2013.10.001.Peer-Reviewed Original ResearchAmyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease
Um JW, Strittmatter SM. Amyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease. Prion 2013, 7: 37-41. PMID: 22987042, PMCID: PMC3609048, DOI: 10.4161/pri.22212.Peer-Reviewed Original ResearchConceptsCellular prion proteinPrion proteinSignal transduction downstreamTransduction downstreamAlzheimer's diseaseFyn kinaseFunctional consequencesAβ oligomersAmyloid-β OligomersNeuronal surfaceHigh-affinity receptorOligomer complexesAD-related phenotypesCentral roleProteinAD pathogenesisRecent evidencePrevalent causeTherapeutic interventionsFynKinaseOligomersPhenotypeDiseaseDownstream
2009
An Unbiased Expression Screen for Synaptogenic Proteins Identifies the LRRTM Protein Family as Synaptic Organizers
Linhoff MW, Laurén J, Cassidy RM, Dobie FA, Takahashi H, Nygaard HB, Airaksinen MS, Strittmatter SM, Craig AM. An Unbiased Expression Screen for Synaptogenic Proteins Identifies the LRRTM Protein Family as Synaptic Organizers. Neuron 2009, 61: 734-749. PMID: 19285470, PMCID: PMC2746109, DOI: 10.1016/j.neuron.2009.01.017.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCells, CulturedCloning, MolecularCricetinaeCricetulusDisks Large Homolog 4 ProteinEmbryo, MammalianGene ExpressionGene Expression RegulationGene LibraryGenetic TestingGuanylate KinasesHippocampusHumansIntracellular Signaling Peptides and ProteinsLuminescent ProteinsMembrane PotentialsMembrane ProteinsMiceMice, KnockoutNeuronsPatch-Clamp TechniquesPDZ DomainsPresynaptic TerminalsRatsSynapsesTransfectionVesicular Glutamate Transport Protein 1ConceptsExpression screenSynaptogenic proteinsTrans-synaptic signalingDomain proteinsProtein familyTransmembrane proteinCDNA libraryMolecular basisSynaptogenic activityPresynaptic differentiationVesicular glutamate transporter VGLUT1Postsynaptic differentiationSynaptic organizersSynapse developmentPositive clonesCocultures of neuronsReported linkageLRRTMsCellular basisProteinGlutamate transporter VGLUT1LRRTM1Synaptic functionCurrent understandingAltered distribution
2008
Release of MICAL Autoinhibition by Semaphorin-Plexin Signaling Promotes Interaction with Collapsin Response Mediator Protein
Schmidt EF, Shim SO, Strittmatter SM. Release of MICAL Autoinhibition by Semaphorin-Plexin Signaling Promotes Interaction with Collapsin Response Mediator Protein. Journal Of Neuroscience 2008, 28: 2287-2297. PMID: 18305261, PMCID: PMC2846290, DOI: 10.1523/jneurosci.5646-07.2008.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCell Adhesion MoleculesCell Line, TransformedChick EmbryoCytoskeletal ProteinsFlavin-Adenine DinucleotideGanglia, SpinalGenetic VectorsHIVHumansImmunoprecipitationIntracellular Signaling Peptides and ProteinsLIM Domain ProteinsMembrane GlycoproteinsMicrofilament ProteinsMixed Function OxygenasesMutationNerve Tissue ProteinsNeuritesNeuronsPeptide FragmentsProtein BindingSemaphorin-3ASemaphorinsSignal TransductionTransfectionConceptsCollapsin response mediator proteinsMediator proteinsCytoplasmic proteinsEnzymatic domainsCatalytic domainPlexin functionPlexin receptorsTerminal domainMICALPromotes interactionAxon guidanceNeuronal developmentAxonal guidanceEnzymatic activityProteinAutoinhibitionDomainPlexinsSignalingSemaphorinsActivatorAssociatesInteractionActivityActivation
2007
The reticulons: a family of proteins with diverse functions
Yang YS, Strittmatter SM. The reticulons: a family of proteins with diverse functions. Genome Biology 2007, 8: 234. PMID: 18177508, PMCID: PMC2246256, DOI: 10.1186/gb-2007-8-12-234.Peer-Reviewed Original ResearchConceptsDiverse functionsEndoplasmic reticulum-Golgi traffickingReticulon homology domainMembrane-associated proteinsAmino-terminal domainFamily of proteinsEukaryotic kingdomsMembrane morphogenesisHomology domainHydrophilic loopReticulon 4Reticulon familyReticulonsDiversity of structuresExpression patternsVesicle formationEndoplasmic reticulumAmino acidsCell surfaceHydrophobic regionAxon growthDiverse groupNeurodegenerative diseasesProteinAmyotrophic lateral sclerosis
2006
RanBPM Contributes to Semaphorin3A Signaling through Plexin-A Receptors
Togashi H, Schmidt EF, Strittmatter SM. RanBPM Contributes to Semaphorin3A Signaling through Plexin-A Receptors. Journal Of Neuroscience 2006, 26: 4961-4969. PMID: 16672672, PMCID: PMC2846289, DOI: 10.1523/jneurosci.0704-06.2006.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCell Adhesion MoleculesCell DeathCell SizeCells, CulturedChick EmbryoCloning, MolecularCricetinaeCricetulusCytoskeletal ProteinsDose-Response Relationship, DrugDrug InteractionsEnzyme InhibitorsGanglia, SpinalGene ExpressionGreen Fluorescent ProteinsHumansImmunoprecipitationIn Situ Nick-End LabelingNerve Tissue ProteinsNeuritesNeuronsNeuropilin-1Nuclear ProteinsRan GTP-Binding ProteinSemaphorin-3ASignal TransductionTranscription Factor AP-1TransfectionTwo-Hybrid System TechniquesConceptsPlexin-A1Collapsin response mediator proteinsNervous system developmentReceptor complex consistingSignal transductionRanBPMMediator proteinsMicrotubule functionCell spreadingComplex consistingAxonal guidanceNeuronal cellsAxonal guidance cuesProteinGuidance cuesPlexinsAxonal outgrowthExpressionSema3ATransductionReceptorsDomainOverexpressionNeuropilinsSystem development
2004
RGM and its receptor neogenin regulate neuronal survival
Matsunaga E, Tauszig-Delamasure S, Monnier PP, Mueller BK, Strittmatter SM, Mehlen P, Chédotal A. RGM and its receptor neogenin regulate neuronal survival. Nature Cell Biology 2004, 6: 749-755. PMID: 15258591, DOI: 10.1038/ncb1157.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAvian ProteinsCaspasesCell SurvivalCells, CulturedChick EmbryoChickensDown-RegulationEnzyme ActivationGene Expression Regulation, DevelopmentalGreen Fluorescent ProteinsImmunohistochemistryIn Situ HybridizationLuminescent ProteinsMembrane ProteinsMutagenesis, Site-DirectedNeuronsRatsRNA, Small InterferingConceptsRepulsive guidance moleculeNeural tubePro-apoptotic activityAxon guidance proteinCytoplasmic domainImmortalized neuronal cellsGene transfer technologyDependence receptorsCell deathGuidance proteinsNeuronal cellsNeogenin receptorGuidance moleculesNeuronal survivalRetinal axonsChick embryosNeogeninReceptor neogeninExpressionCaspasesReceptorsTransfer technologyEmbryosProteinApoptosis
2003
Structural bases for CRMP function in plexin‐dependent semaphorin3A signaling
Deo RC, Schmidt EF, Elhabazi A, Togashi H, Burley SK, Strittmatter SM. Structural bases for CRMP function in plexin‐dependent semaphorin3A signaling. The EMBO Journal 2003, 23: 9-22. PMID: 14685275, PMCID: PMC1271659, DOI: 10.1038/sj.emboj.7600021.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmino Acid SequenceAmino Acid SubstitutionAnimalsCell Adhesion MoleculesCell LineChick EmbryoChlorocebus aethiopsCOS CellsCrystallography, X-RayGanglia, SpinalHumansHydrogen BondingImmunophilinsMiceModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedNerve Tissue ProteinsPhosphoproteinsProtein Structure, SecondaryProtein Structure, TertiaryReceptors, Cell SurfaceRecombinant Fusion ProteinsSemaphorin-3ASequence Homology, Amino AcidSignal TransductionStructure-Activity RelationshipConceptsCollapsin response mediator proteinsStructure-based mutagenesisCOS-7 cellsSurface-exposed residuesTetrameric assemblyPhysical complexAxonal specificationMediator proteinsStructural basisFunctional domainsAlanine substitutionsActive proteinCytosolic phosphoproteinNeuronal differentiationAxonal repulsionAxonal guidanceReceptor componentsProteinStructural viewX-ray crystal structureCRMP1Sema3ACell contractionCellsNP1
1999
Go protein-dependent survival of primary accessory olfactory neurons
Tanaka M, Treloar H, Kalb R, Greer C, Strittmatter S. Go protein-dependent survival of primary accessory olfactory neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 14106-14111. PMID: 10570206, PMCID: PMC24198, DOI: 10.1073/pnas.96.24.14106.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Adhesion Molecules, NeuronalCell SurvivalCells, CulturedFemaleGTP-Binding Protein alpha Subunit, Gi2GTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, Gi-GoHeterotrimeric GTP-Binding ProteinsHumansMaleMiceMice, Inbred C57BLMice, KnockoutNeural Cell Adhesion MoleculesNeuronsProto-Oncogene ProteinsProto-Oncogene Proteins c-fosRatsSynaptophysinVomeronasal OrganConceptsPosterior accessory olfactory bulbCell survivalAccessory olfactory bulbG proteinsOlfactory systemAccessory olfactory systemG protein-independent processReceptor-coupled G proteinsG protein-coupled receptor familyProtein-coupled receptor familyVNO neuronsAxonal targetingSensory functionAxonal guidanceReceptor familyAnterior accessory olfactory bulbTargeted deletionOlfactory neuronsReceptor neuronsC-Fos immunoreactivityProteinApoptotic neuronsNeurons decreasesOlfactory bulbSensory activationA PDZ Protein Regulates the Distribution of the Transmembrane Semaphorin, M-SemF*
Wang L, Kalb R, Strittmatter S. A PDZ Protein Regulates the Distribution of the Transmembrane Semaphorin, M-SemF*. Journal Of Biological Chemistry 1999, 274: 14137-14146. PMID: 10318831, DOI: 10.1074/jbc.274.20.14137.Peer-Reviewed Original ResearchConceptsPDZ proteinsG-protein signal transduction pathwaySingle PDZ domainDetergent-resistant aggregatesSignal transduction pathwaysAxon guidance signalsPDZ domainCytoplasmic domainProtein interactionsTransduction pathwaysTransmembrane semaphorinsExpression studiesFour residuesGAIPSubcellular distributionHEK293 cellsSemaphorin familyCell surfaceProteinNeural proteinsGuidance signalsInteractsGIPCPDZSemaphorins
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
1995
Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33
Goshima Y, Nakamura F, Strittmatter P, Strittmatter S. Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33. Nature 1995, 376: 509-514. PMID: 7637782, DOI: 10.1038/376509a0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBrainCaenorhabditis elegans ProteinsCell LineCell MembraneChick EmbryoGanglia, SpinalGlycoproteinsGTP-Binding ProteinsHelminth ProteinsIntercellular Signaling Peptides and ProteinsMolecular Sequence DataNerve Growth FactorsNerve Tissue ProteinsNeuritesNeuronsOocytesRecombinant Fusion ProteinsSemaphorin-3ASignal TransductionVirulence Factors, BordetellaXenopus laevisConceptsGrowth cone collapseDorsal root ganglion neuronsCollapsin response mediator proteinsCone collapseXenopus laevis oocyte expression systemChick nervous systemGanglion neuronsNervous systemOocyte expression systemUNC-33Inward currentsNeuronal proteinsAxonal pathfindingNeural developmentX. laevis oocytesGrowth conesLaevis oocytesIntracellular proteinsHeterotrimeric GTPMediator proteinsProteinIntracellular componentsNeurons