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 domainsSpeciesDomainProteinAβOsHuman neuroepithelial stem cell regional specificity enables spinal cord repair through a relay circuit
Dell’Anno M, Wang X, Onorati M, Li M, Talpo F, Sekine Y, Ma S, Liu F, Cafferty WBJ, Sestan N, Strittmatter SM. Human neuroepithelial stem cell regional specificity enables spinal cord repair through a relay circuit. Nature Communications 2018, 9: 3419. PMID: 30143638, PMCID: PMC6109094, DOI: 10.1038/s41467-018-05844-8.Peer-Reviewed Original ResearchConceptsHuman neuroepithelial stem cellsNeuroepithelial stem cellsSpinal cord injury recoverySpinal cord injury resultsNeural stem cell transplantationStem cell transplantationSpinal cord repairOptimal cell typeStem cellsGrafted neuronsPersistent disabilityFunctional recoveryTherapeutic optionsCell transplantationHost axonsInjury resultsSpinal cordRobust engraftmentImmunodeficient miceInjury recoveryAnatomical sitesNeural elementsSpecific marker proteinsTransplantationAdherent conditions
2015
Intravitreal Delivery of Human NgR-Fc Decoy Protein Regenerates Axons After Optic Nerve Crush and Protects Ganglion Cells in Glaucoma ModelsNgR-Fc Rescues Ganglion Cells in Glaucoma
Wang X, Lin J, Arzeno A, Choi JY, Boccio J, Frieden E, Bhargava A, Maynard G, Tsai JC, Strittmatter SM. Intravitreal Delivery of Human NgR-Fc Decoy Protein Regenerates Axons After Optic Nerve Crush and Protects Ganglion Cells in Glaucoma ModelsNgR-Fc Rescues Ganglion Cells in Glaucoma. Investigative Ophthalmology & Visual Science 2015, 56: 1357-1366. PMID: 25655801, PMCID: PMC4338631, DOI: 10.1167/iovs.14-15472.Peer-Reviewed Original ResearchConceptsOptic nerve crushFluro-GoldNerve crushAxonal regenerationGanglion cellsOptic nerve crush injuryRetinal ganglion cell degenerationRGC axonal regenerationNerve crush injuryDisease-modifying therapiesGanglion cell degenerationDecoy proteinMicrobead modelVitreal spaceIntravitreal treatmentRGC densityAxonal sproutingCrush injuryGlaucoma modelNeuroprotective effectsAnterior chamberControl ratsVision lossAnterograde labelingBolus administration
2012
Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons
Um JW, Nygaard HB, Heiss JK, Kostylev MA, Stagi M, Vortmeyer A, Wisniewski T, Gunther EC, Strittmatter SM. Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nature Neuroscience 2012, 15: 1227-1235. PMID: 22820466, PMCID: PMC3431439, DOI: 10.1038/nn.3178.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBlotting, WesternCalcium SignalingCell LineDendritic SpinesElectroencephalographyEnzyme ActivationHumansMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicNeuronsPhosphorylationProtein BindingProto-Oncogene Proteins c-fynPrPC ProteinsRatsReceptors, N-Methyl-D-AspartateSeizuresSynapses
2011
Cartilage Acidic Protein–1B (LOTUS), an Endogenous Nogo Receptor Antagonist for Axon Tract Formation
Sato Y, Iketani M, Kurihara Y, Yamaguchi M, Yamashita N, Nakamura F, Arie Y, Kawasaki T, Hirata T, Abe T, Kiyonari H, Strittmatter SM, Goshima Y, Takei K. Cartilage Acidic Protein–1B (LOTUS), an Endogenous Nogo Receptor Antagonist for Axon Tract Formation. Science 2011, 333: 769-773. PMID: 21817055, PMCID: PMC3244695, DOI: 10.1126/science.1204144.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBinding SitesCalcium-Binding ProteinsCell LineCells, CulturedGPI-Linked ProteinsGrowth ConesHumansImmunohistochemistryLigandsMiceMice, Inbred ICRMyelin ProteinsNogo ProteinsNogo Receptor 1Olfactory PathwaysProsencephalonProtein BindingReceptors, Cell SurfaceSignal TransductionConceptsTract formationNogo receptor 1Axon growth inhibitorsProtein 1BEndogenous antagonismAxon tract formationReceptor antagonistGrowth cone collapseAxonal projectionsCircuitry formationNeural circuitry formationMouse brainReceptor 1LOT formationNeural regenerationNgR1Key moleculesCone collapseMiceFluorophore-assisted light inactivationGrowth inhibitorAntagonistBrainMyelinNogo
2006
Alzheimer Precursor Protein Interaction with the Nogo-66 Receptor Reduces Amyloid-β Plaque Deposition
Park JH, Gimbel DA, GrandPre T, Lee JK, Kim JE, Li W, Lee DH, Strittmatter SM. Alzheimer Precursor Protein Interaction with the Nogo-66 Receptor Reduces Amyloid-β Plaque Deposition. Journal Of Neuroscience 2006, 26: 1386-1395. PMID: 16452662, PMCID: PMC2846286, DOI: 10.1523/jneurosci.3291-05.2006.Peer-Reviewed Original ResearchConceptsAmyloid precursor proteinAlzheimer's diseaseAbeta levelsDystrophic neuritesPlaque depositionAmyloid-β plaque depositionCourse of ADAbeta plaque depositionTransgenic AD modelBrain Abeta levelsAD brain samplesAdult CNS axonsAxonal sprouting responseNgR expressionAbeta depositsAxonal dysfunctionPathophysiologic hypothesesSecretase processingTraumatic injuryAbeta productionDisease processAD modelBrain samplesCNS axonsPlaque deposits
2005
Nogo-A Interacts with the Nogo-66 Receptor through Multiple Sites to Create an Isoform-Selective Subnanomolar Agonist
Hu F, Liu BP, Budel S, Liao J, Chin J, Fournier A, Strittmatter SM. Nogo-A Interacts with the Nogo-66 Receptor through Multiple Sites to Create an Isoform-Selective Subnanomolar Agonist. Journal Of Neuroscience 2005, 25: 5298-5304. PMID: 15930377, PMCID: PMC2855126, DOI: 10.1523/jneurosci.5235-04.2005.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseAnimalsAxonsBinding SitesCell LineChick EmbryoChlorocebus aethiopsGlutathione TransferaseGPI-Linked ProteinsHumansIn Vitro TechniquesLigandsMiceMyelin ProteinsNogo ProteinsNogo Receptor 1PeptidesProtein IsoformsProtein Structure, TertiaryReceptors, Cell SurfaceRecombinant Fusion Proteins
2004
Neogenin mediates the action of repulsive guidance molecule
Rajagopalan S, Deitinghoff L, Davis D, Conrad S, Skutella T, Chedotal A, Mueller BK, Strittmatter SM. Neogenin mediates the action of repulsive guidance molecule. Nature Cell Biology 2004, 6: 756-762. PMID: 15258590, DOI: 10.1038/ncb1156.Peer-Reviewed Original ResearchConceptsRepulsive guidance moleculeRetinal ganglion cell axonsGuidance moleculesGanglion cell axonsDorsal root ganglion axonsTemporal retinal axonsVisual map formationReceptor mechanismsCell axonsNeogenin expressionRetinal axonsGanglion axonsAxonal responsivenessOptic tectumChick retinaNeogeninSub-nanomolar affinityAxonsAxonal guidanceNeogenin functionsResponsive stateNeural tubeMap formationExpressionRetinaA new role for Nogo as a regulator of vascular remodeling
Acevedo L, Yu J, Erdjument-Bromage H, Miao RQ, Kim JE, Fulton D, Tempst P, Strittmatter SM, Sessa WC. A new role for Nogo as a regulator of vascular remodeling. Nature Medicine 2004, 10: 382-388. PMID: 15034570, DOI: 10.1038/nm1020.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsVascular remodelingMuscle cellsVascular smooth muscle cellsCentral nervous systemIntact blood vesselsVascular injuryAxonal regenerationNeointimal proliferationMice promotesKnockout miceNervous systemVascular homeostasisFamily of proteinsVascular expansionEndothelial cellsBlood vesselsNogoNogo isoformsLipid raftsProteomic analysisN-terminusRemodelingGene transferCells
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
2002
Truncated Soluble Nogo Receptor Binds Nogo-66 and Blocks Inhibition of Axon Growth by Myelin
Fournier AE, Gould GC, Liu BP, Strittmatter SM. Truncated Soluble Nogo Receptor Binds Nogo-66 and Blocks Inhibition of Axon Growth by Myelin. Journal Of Neuroscience 2002, 22: 8876-8883. PMID: 12388594, PMCID: PMC6757674, DOI: 10.1523/jneurosci.22-20-08876.2002.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAxonsCell LineChick EmbryoGPI-Linked ProteinsGrowth ConesHumansKidneyMiceMolecular Sequence DataMutagenesis, Site-DirectedMyelin ProteinsMyelin SheathNeuritesNogo ProteinsNogo Receptor 1Peptide FragmentsProtein BindingProtein Structure, TertiaryReceptors, Cell SurfaceRepetitive Sequences, Amino AcidRetinaSequence DeletionSignal TransductionSolubilityConceptsChick retinal ganglion cellsRetinal ganglion cellsOutgrowth inhibitionMechanism of NogoGanglion cellsNogo receptorOutgrowth inhibitorViral infectionMyelin inhibitionInhibitory signalingNogo-66Axon growthCNS myelinAxon outgrowthMyelinRegenerative growthNogoCOS-7 cellsInhibitionAlkaline phosphataseReceptorsNGR
2001
Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration
Fournier A, GrandPre T, Strittmatter S. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 2001, 409: 341-346. PMID: 11201742, DOI: 10.1038/35053072.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsAxonsBinding SitesCell DivisionCell LineChickensCloning, MolecularCOS CellsDNA, ComplementaryGene ExpressionGPI-Linked ProteinsGrowth ConesHumansMiceMolecular Sequence DataMyelin ProteinsNerve RegenerationNogo ProteinsNogo Receptor 1Protein Structure, TertiaryReceptors, Cell SurfaceRecombinant Fusion ProteinsConceptsNogo-66Axonal regenerationHuman CNS injuryNogo-66 receptorAxonal inhibitionAdult vertebrate CNSUnresponsive neuronsCentral nervous system myelinCNS injuryReceptor expressionAxon regenerationEnhanced recoveryGlycophosphatidylinositol-linked proteinAxonal extensionNogoNeuronsReceptorsSystem myelinAxonal surfaceInhibitionCell typesVertebrate CNSExtracellular domainHigh affinityCell morphology
2000
Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein
GrandPré T, Nakamura F, Vartanian T, Strittmatter S. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature 2000, 403: 439-444. PMID: 10667797, DOI: 10.1038/35000226.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAxonsCattleCell DivisionCell LineCentral Nervous SystemChick EmbryoCloning, MolecularConsensus SequenceEscherichia coliGrowth InhibitorsHumansMembrane ProteinsMolecular Sequence DataMyelin ProteinsNerve RegenerationNogo ProteinsOligodendrogliaPC12 CellsRatsRecombinant ProteinsSequence Homology, Amino AcidConceptsCentral nervous systemPeripheral nervous systemCNS white matterAxonal regenerationAxon regenerationNervous systemWhite matterAdult central nervous systemMammalian axon regenerationIN-1 antibodiesReticulon 1Dorsal root ganglion growth conesFunctional recoverySpinal cordSchwann cellsCNS axonsExtracellular domainAxonal extensionNogoAxon extensionGrowth conesOligodendrocytesInhibitory activityReticulon 4Moderate degree
1999
A 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
1998
Neuropilin-1 Extracellular Domains Mediate Semaphorin D/III-Induced Growth Cone Collapse
Nakamura F, Tanaka M, Takahashi T, Kalb R, Strittmatter S. Neuropilin-1 Extracellular Domains Mediate Semaphorin D/III-Induced Growth Cone Collapse. Neuron 1998, 21: 1093-1100. PMID: 9856464, DOI: 10.1016/s0896-6273(00)80626-1.Peer-Reviewed Original ResearchSemaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin-2 receptors
Takahashi T, Nakamura F, Jin Z, Kalb R, Strittmatter S. Semaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin-2 receptors. Nature Neuroscience 1998, 1: 487-493. PMID: 10196546, DOI: 10.1038/2203.Peer-Reviewed Original Research
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
1994
Activated mutants of the alpha subunit of G(o) promote an increased number of neurites per cell
Strittmatter S, Fishman M, Zhu X. Activated mutants of the alpha subunit of G(o) promote an increased number of neurites per cell. Journal Of Neuroscience 1994, 14: 2327-2338. PMID: 8158271, PMCID: PMC6577129, DOI: 10.1523/jneurosci.14-04-02327.1994.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCell LineChlorocebus aethiopsDNA PrimersDose-Response Relationship, DrugGTP-Binding ProteinsIntercellular Signaling Peptides and ProteinsKineticsMacromolecular SubstancesMolecular Sequence DataMutagenesis, Site-DirectedNeuritesNeuroblastomaPC12 CellsPeptidesPertussis ToxinPoint MutationTransfectionTumor Cells, CulturedVirulence Factors, BordetellaWasp VenomsConceptsAlpha oNumber of neuritesPertussis toxin-sensitive G proteinToxin-sensitive G proteinGrowth conesAlpha subunitG proteinsNeurite outgrowthTotal neurite lengthN1E-115 cellsAlpha i2Activated alpha subunitNeuroblastoma cellsNeurite numberNeurite lengthNeuronal growth conesAlpha sOncogenic mutationsActivation stateO mutantsActivationNeuritesCellsPoint mutationsSubunitsAn amino-terminal domain of the growth-associated protein gap-43 mediates its effects on filopodial formation and cell spreading
Strittmatter S, Valenzuela D, Fishman M. An amino-terminal domain of the growth-associated protein gap-43 mediates its effects on filopodial formation and cell spreading. Journal Of Cell Science 1994, 107: 195-204. PMID: 8175908, DOI: 10.1242/jcs.107.1.195.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCarcinoma, Squamous CellCell LineCell MembraneCell MovementChlorocebus aethiopsColforsinCyclic AMPGAP-43 ProteinGene ExpressionGenetic VectorsGrowth SubstancesHumansMembrane GlycoproteinsMolecular Sequence DataNerve Tissue ProteinsNeuronsPlasmidsSequence DeletionStructure-Activity RelationshipTransfectionTumor Cells, CulturedConceptsAmino-terminal domainCell shapeAmino terminusFusion proteinA431 cellsCell shape changesCOS-7 cellsProtein kinase CGrowth cone membraneCell surface activityLevel of forskolinMutant proteinsHeterotrimeric GTPNon-neuronal cellsG protein stimulationProtein mutantsChimeric geneGAP-43Filopodial formationFunctional domainsCell spreadingBind calmodulinKinase CMajor substratePeptide stretch
1993
Functional expression of sodium channel mutations identified in families with periodic paralysis
Cannon S, Strittmatter S. Functional expression of sodium channel mutations identified in families with periodic paralysis. Neuron 1993, 10: 317-326. PMID: 8382500, DOI: 10.1016/0896-6273(93)90321-h.Peer-Reviewed Original ResearchConceptsSodium channel alpha subunitChannel alpha subunitAlpha subunitFunctional expressionMammalian cell linesSame functional defectSodium channel mutationsBenign polymorphismsSingle-channel conductanceMutationsChannel mutationsCell linesSubunitsMyotubesFunctional defectsPeriodic paralysisProcess of inactivationPotassium dependenceNoninactivating componentNew regionsInactivationExpressionPolymorphismSodium currentFamily