2024
Ectopic reconstitution of a spine-apparatus-like structure provides insight into mechanisms underlying its formation
Falahati H, Wu Y, Fang M, De Camilli P. Ectopic reconstitution of a spine-apparatus-like structure provides insight into mechanisms underlying its formation. Current Biology 2024, 35: 265-276.e4. PMID: 39626668, PMCID: PMC11753949, DOI: 10.1016/j.cub.2024.11.010.Peer-Reviewed Original ResearchEndoplasmic reticulumSpine apparatusActin bundlesEndomembrane networkER sheetsConserved regionProtein synaptopodinCisternal organelleNon-neuronal cellsER cisternsOrganellesSynaptopodinProteinNeuronal dendritesNeuronal spinesAxon initial segmentFindings shed lightBiogenesisActinProtein matrixNarrow lumenReticulumMammalsInitial segmentMechanismDisease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons
Wu J, Quraishi I, Zhang Y, Bromwich M, Kaczmarek L. Disease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons. Cell Reports 2024, 43: 113904. PMID: 38457342, PMCID: PMC11013952, DOI: 10.1016/j.celrep.2024.113904.Peer-Reviewed Original ResearchInhibitory neuronsRegulation of neuronal excitabilityPotassium channel mutationsVoltage-dependent sodiumInhibitory cortical neuronsGain-of-function mutationsAxon initial segmentKCNT1 geneNeuronal excitabilityChannel subunitsChannel mutationsNetwork hyperexcitabilityMouse modelNeuron typesCortical neuronsTreat epilepsyNeuronsExcitable neuronsNeurological disordersSevere intellectual disabilityMutationsInitial segmentKCNT1ExpressionHyperexcitability
2022
Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines
Falahati H, Wu Y, Feuerer V, Simon HG, De Camilli P. Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2203750119. PMID: 36215465, PMCID: PMC9586327, DOI: 10.1073/pnas.2203750119.Peer-Reviewed Original ResearchConceptsSpine apparatusDendritic spinesSubset of neuronsAxon initial segmentDendritic shaftsER cisternsNonneuronal cellsSynaptopodinSpineSmooth endoplasmic reticulumEndoplasmic reticulumCisternal organelleInitial segmentSpecific localizationCisternsBinding proteinPDLIM7Expression patternsSubsetProteinSmall subsetDiseaseNeuronsBrainFunctional partnership
2020
Whole-Cell Photobleaching Reveals Time-Dependent Compartmentalization of Soluble Proteins by the Axon Initial Segment
Nicholson L, Gervasi N, Falières T, Leroy A, Miremont D, Zala D, Hanus C. Whole-Cell Photobleaching Reveals Time-Dependent Compartmentalization of Soluble Proteins by the Axon Initial Segment. Frontiers In Cellular Neuroscience 2020, 14: 180. PMID: 32754013, PMCID: PMC7366827, DOI: 10.3389/fncel.2020.00180.Peer-Reviewed Original ResearchSoluble proteinAxon initial segmentCytoplasmic soluble proteinsForm of compartmentalizationIntact F-actinSuper-resolution fluorescence imagingSpectrin cytoskeletonSpecific proteinsF-actinProtein accumulationAxonal compartmentProtein exchangeProteinCompartmentalizationSomatodendritic compartmentNeuronal morphologyInitial segmentImportant insightsUltrastructureCompartmentsFluorescence imagingPhotobleachingCytoskeletonSignalingDifferentiation
2019
Neurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly
Yang R, Walder-Christensen KK, Lalani S, Yan H, García-Prieto ID, Álvarez S, Fernández-Jaén A, Speltz L, Jiang YH, Bennett V. Neurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 19717-19726. PMID: 31451636, PMCID: PMC6765234, DOI: 10.1073/pnas.1909989116.Peer-Reviewed Original ResearchConceptsΒ4-spectrinAxon initial segmentC-terminal domainNormal neural developmentPrevents recruitmentGiant ankyrinNeural developmentConformational changesMissense mutationsMutationsPhosphorylationSegment assemblyRecruitmentMouse brainClose appositionCore mechanismDomainAssemblyAnkyrinClosed configurationIntermediate stageInitial segmentSitesProximal axons
2014
Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy
Oliva MK, McGarr TC, Beyer BJ, Gazina E, Kaplan DI, Cordeiro L, Thomas E, Dib-Hajj SD, Waxman SG, Frankel WN, Petrou S. Physiological and genetic analysis of multiple sodium channel variants in a model of genetic absence epilepsy. Neurobiology Of Disease 2014, 67: 180-190. PMID: 24657915, PMCID: PMC4298829, DOI: 10.1016/j.nbd.2014.03.007.Peer-Reviewed Original Research
2013
An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier
Breslow DK, Koslover EF, Seydel F, Spakowitz AJ, Nachury MV. An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier. Journal Of Cell Biology 2013, 203: 129-147. PMID: 24100294, PMCID: PMC3798247, DOI: 10.1083/jcb.201212024.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsCell LineCell MembraneCell Membrane PermeabilityCiliaDiffusionMiceMicroscopy, FluorescenceMicroscopy, VideoModels, BiologicalMolecular WeightNuclear PoreProtein TransportProteinsRecombinant Fusion ProteinsReproducibility of ResultsTime FactorsTime-Lapse ImagingTransfectionConceptsNuclear pore complexCiliary diffusion barrierPore complexActin cytoskeletonMembrane proteinsActive transportPrimary ciliaPlasma membraneCiliary membraneSpecific proteinsLarge proteinsMechanistic basisPermeabilized cellsProteinCiliaAxon initial segmentMembraneCellsCytoskeletonInitial segmentEntryTransportAssaysVivoComplexes
2012
An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier
Gasser A, Ho TS, Cheng X, Chang KJ, Waxman SG, Rasband MN, Dib-Hajj SD. An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier. Journal Of Neuroscience 2012, 32: 7232-7243. PMID: 22623668, PMCID: PMC3413458, DOI: 10.1523/jneurosci.5434-11.2012.Peer-Reviewed Original ResearchConceptsReporter proteinAxon initial segmentKinase phosphorylation siteSodium channelsIntracellular loop 2Nodes of RanvierFull-length channelGlutamic acid residuesPhosphorylation sitesMechanism of channelVoltage-gated sodium channelsAcid residuesLoop 2Functional mouseNav1.6 sodium channelsMotifProteinVivo analysisAnkyrinGSomatodendritic compartmentCultured neuronsInitial segmentVivoAction potentialsCellsA Distal Axonal Cytoskeleton Forms an Intra-Axonal Boundary that Controls Axon Initial Segment Assembly
Galiano MR, Jha S, Ho TS, Zhang C, Ogawa Y, Chang KJ, Stankewich MC, Mohler PJ, Rasband MN. A Distal Axonal Cytoskeleton Forms an Intra-Axonal Boundary that Controls Axon Initial Segment Assembly. Cell 2012, 149: 1125-1139. PMID: 22632975, PMCID: PMC3361702, DOI: 10.1016/j.cell.2012.03.039.Peer-Reviewed Original Research
2011
The spatio‐temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study
Popovic MA, Foust AJ, McCormick DA, Zecevic D. The spatio‐temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study. The Journal Of Physiology 2011, 589: 4167-4187. PMID: 21669974, PMCID: PMC3180577, DOI: 10.1113/jphysiol.2011.209015.Peer-Reviewed Original ResearchConceptsSpike trigger zoneAction potential initiationAxon initial segmentTrigger zoneLayer 5 pyramidal neuronsPotential initiationLayer 5 pyramidal cellsMature axonsPyramidal neuronsAxonal collateralsPyramidal cellsNeuronal plasticityAction potentialsImmature axonsPotential imaging techniqueAxonsImmunocytochemical dataNeuronal computationSaltatory conductionAP propagationElectrophysiological measuresInitial segmentImaging techniquesCritical roleInitiation
2010
Action Potentials Initiate in the Axon Initial Segment and Propagate through Axon Collaterals Reliably in Cerebellar Purkinje Neurons
Foust A, Popovic M, Zecevic D, McCormick DA. Action Potentials Initiate in the Axon Initial Segment and Propagate through Axon Collaterals Reliably in Cerebellar Purkinje Neurons. Journal Of Neuroscience 2010, 30: 6891-6902. PMID: 20484631, PMCID: PMC2990270, DOI: 10.1523/jneurosci.0552-10.2010.Peer-Reviewed Original ResearchConceptsAxon initial segmentAxon collateralsAction potentialsPurkinje neuronsComplex spikesLocal axon collateralsCerebellar Purkinje neuronsInitial segmentFast action potentialsAxon branch pointsSynaptic inputsVoltage-sensitive dyeCerebellar cortexNeuronal processingSpike initiationDischarge frequencySingle trialCollateralsOutput cellsNeurons
2008
Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics
Yu Y, Shu Y, McCormick DA. Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics. Journal Of Neuroscience 2008, 28: 7260-7272. PMID: 18632930, PMCID: PMC2664555, DOI: 10.1523/jneurosci.1613-08.2008.Peer-Reviewed Original ResearchConceptsAxon initial segmentAction potentialsAction potential backpropagationAction potential outputAction potential responsesThreshold variabilityInitial segmentCortical neuronsSynaptic activitySynaptic inputsSomatic recordingsCortical ensemblesSensorimotor integrationRate variabilityAction potential eventsSpike initiationAmplitude-time courseTime courseHigh rateTrial variabilityNeurons
2006
Properties of Action-Potential Initiation in Neocortical Pyramidal Cells: Evidence From Whole Cell Axon Recordings
Shu Y, Duque A, Yu Y, Haider B, McCormick D. Properties of Action-Potential Initiation in Neocortical Pyramidal Cells: Evidence From Whole Cell Axon Recordings. Journal Of Neurophysiology 2006, 97: 746-760. PMID: 17093120, DOI: 10.1152/jn.00922.2006.Peer-Reviewed Original ResearchConceptsCortical pyramidal cellsAction potential initiationAxon initial segmentPyramidal cellsAction potentialsSynaptic activityLayer 5 pyramidal neuronsSimultaneous whole-cell recordingsWhole-cell recordingsNeocortical pyramidal cellsRecurrent network activityAction potential generationInitial segmentIntradendritic injectionPyramidal neuronsApical dendritesEpileptiform activityCortical neuronsEpileptiform dischargesIntracortical axonsEpileptic seizuresSynaptic bombardmentCell recordingsDistal axonsSynaptic barrages
2000
βiv Spectrin, a New Spectrin Localized at Axon Initial Segments and Nodes of Ranvier in the Central and Peripheral Nervous System
Berghs S, Aggujaro D, Dirkx R, Maksimova E, Stabach P, Hermel J, Zhang J, Philbrick W, Slepnev V, Ort T, Solimena M. βiv Spectrin, a New Spectrin Localized at Axon Initial Segments and Nodes of Ranvier in the Central and Peripheral Nervous System. Journal Of Cell Biology 2000, 151: 985-1002. PMID: 11086001, PMCID: PMC2174349, DOI: 10.1083/jcb.151.5.985.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnkyrinsAutoantigensAxonsBlood ProteinsBrain ChemistryChromosomesCloning, MolecularCOS CellsCytoplasmCytoskeletonDiabetic NeuropathiesGene ExpressionHippocampusHumansIslets of LangerhansMaleMembrane ProteinsMiceMolecular Sequence DataNerve Tissue ProteinsPhosphoproteinsProtein Structure, TertiaryProtein Tyrosine PhosphatasesRanvier's NodesRatsRats, Sprague-DawleyReceptor-Like Protein Tyrosine Phosphatases, Class 8RNA, MessengerSciatic NerveSignal TransductionSodium ChannelsSpectrinConceptsPleckstrin homology domainHomology domainBetaIV spectrinActin-binding domainAxon initial segmentPutative SH3Alternative splicingSpectrin geneSpectrin repeatsDetergent extractabilityCell adhesion moleculeNodes of RanvierSubcellular fractionationTerminal halfAdditional isoformsDistinct isoformsLong isoformNorthern blotSpectrinAbundant expressionΒIV-spectrinIsoformsSpectrin antibodiesEmbryonic day 19Initial segment
1999
A diffusion barrier maintains distribution of membrane proteins in polarized neurons
Winckler B, Forscher P, Mellman I. A diffusion barrier maintains distribution of membrane proteins in polarized neurons. Nature 1999, 397: 698-701. PMID: 10067893, DOI: 10.1038/17806.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsAxonsBiological TransportCell CompartmentationCell MembraneCell PolarityCells, CulturedCytoskeletonDiffusionDimethyl SulfoxideLeukocyte L1 Antigen ComplexMembrane GlycoproteinsMembrane ProteinsMicrospheresNeural Cell Adhesion MoleculesNeuronsRatsReceptors, AMPAThy-1 AntigensConceptsMembrane proteinsDiffusion barrierObvious physical barriersPlasma membrane domainsLateral mobilityOptical tweezersCell-cell contactMembrane domainsPresumptive domainPolarized neuronsPlasma membraneCytoskeletal componentsPolarized distributionF-actinDiffusion of proteinsDistinct domainsBasolateral surfaceMembrane markersProteinSpecialized domainsInitial segmentTight junctionsAsymmetric distributionPhysical barrierTweezers
1984
Angiotensin-Converting Enzyme in the Male Rat Reproductive System: Autoradiographic Visualization with [3H]Captopril*
STRITTMATTER S, SNYDER S. Angiotensin-Converting Enzyme in the Male Rat Reproductive System: Autoradiographic Visualization with [3H]Captopril*. Endocrinology 1984, 115: 2332-2341. PMID: 6094156, DOI: 10.1210/endo-115-6-2332.Peer-Reviewed Original ResearchConceptsACE activityMale rat reproductive systemRat reproductive systemSoluble ACE activityAutoradiographic silver grainsStages I-VIIIInitial segmentMale ratsAutoradiographic visualizationPharmacological profileTesticular slicesBasal epitheliumSilver grainsLuminal labellingReproductive tractInterstitial tissueMonoclonal antibodiesVas deferensSeminiferous tubulesLevel of bindingReproductive systemLuminal surfaceEpithelium
1983
Intracellular and extracellular electrophysiology of nigral dopaminergic neurons—1. Identification and characterization
Grace A, Bunney B. Intracellular and extracellular electrophysiology of nigral dopaminergic neurons—1. Identification and characterization. Neuroscience 1983, 10: 301-315. PMID: 6633863, DOI: 10.1016/0306-4522(83)90135-5.Peer-Reviewed Original ResearchConceptsAction potentialsDopamine neuronsDopamine cellsGlyoxylic acid-induced catecholamine fluorescenceInput resistanceDopamine synthesizing enzymePostsynaptic target areasIntracellular dopamine contentNigral dopamine cellsPossible modulatory effectDopamine-containing cellsIntracellular dopamine concentrationSame inhibitory effectHigh input resistanceInitial segmentAntidromic activationDopaminergic neuronsDopamine contentIntracellular recordingsDopamine synthesisCaudate nucleusElectrophysiological characteristicsTyrosine hydroxylaseCatecholamine fluorescenceModulatory effects
1981
Morphology of regenerated spinal cord in Sternarchus albifrons
Anderson M, Waxman S. Morphology of regenerated spinal cord in Sternarchus albifrons. Cell And Tissue Research 1981, 219: 1-8. PMID: 7285088, DOI: 10.1007/bf00210014.Peer-Reviewed Original ResearchConceptsSpinal cordElectromotor neuronsRegenerated spinal cordCell bodiesSpinal cord correlatesNumerous blood vesselsSite of transectionRostro-caudal gradientSternarchus albifronsLack dendritesRegenerated cordNormal cordGlial cellsPresynaptic axonsEpendymal cellsCordBlood vesselsAxonsNeuronsAnterior sectionNormal morphologyCell relationshipsGap junctionsDistinct tractsInitial segment
1978
Intra-axonal ferric ion-ferrocyanide staining of nodes of Ranvier and initial segments in central myelinated fibers
Waxman S, Quick D. Intra-axonal ferric ion-ferrocyanide staining of nodes of Ranvier and initial segments in central myelinated fibers. Brain Research 1978, 144: 1-10. PMID: 76497, DOI: 10.1016/0006-8993(78)90430-4.Peer-Reviewed Original ResearchConceptsNodes of RanvierInitial segmentFerric ion-ferrocyanide stainingCentral nervous tissueAxon initial segmentCentral myelinated fibersSpinal cordMyelinated fibersNervous tissueMyelinated neuronsAxon hillockCell bodiesNodal axolemmaRanvierNeuronsAxolemmaStainingElectron-dense substanceStainInternodal regionsUltrastructural dataSpecialized regions
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