2024
Phosphoglycerate kinase is a central leverage point in Parkinson’s disease–driven neuronal metabolic deficits
Kokotos A, Antoniazzi A, Unda S, Ko M, Park D, Eliezer D, Kaplitt M, De Camilli P, Ryan T. Phosphoglycerate kinase is a central leverage point in Parkinson’s disease–driven neuronal metabolic deficits. Science Advances 2024, 10: eadn6016. PMID: 39167658, PMCID: PMC11338267, DOI: 10.1126/sciadv.adn6016.Peer-Reviewed Original ResearchConceptsPhosphoglycerate kinase 1Metabolic deficitsExpressions of Phosphoglycerate Kinase 1Dopamine axonsParkinson's diseasePD-associated pathologyViral expressionLoss of functionNeuronal glycolysisSusceptibility lociIn vivoFamilial Parkinson's diseasePD therapeuticsMetabolic lesionsProduction kineticsKinase 1Mitochondrial integrityPhosphoglycerate kinaseBioenergetic deficitsSynaptic dysfunctionGenetic originDeficitsPARK7/DJ-1Phosphoglycerate
2023
End-binding protein 1 promotes specific motor-cargo association in the cell body prior to axonal delivery of dense core vesicles
Park J, Xie Y, Miller K, De Camilli P, Yogev S. End-binding protein 1 promotes specific motor-cargo association in the cell body prior to axonal delivery of dense core vesicles. Current Biology 2023, 33: 3851-3864.e7. PMID: 37586371, PMCID: PMC10529979, DOI: 10.1016/j.cub.2023.07.052.Peer-Reviewed Original ResearchConceptsKIF1A/UNCTrans-GolgiDense-core vesiclesEnd-binding protein 1Microtubule growthEnd-binding protein EB1Calponin homology domainMicrotubule-associated proteinsDCV biogenesisCore vesiclesSorting machineryHomology domainAxonal deliveryProtein EB1DCV cargosEndogenous cargoUnrelated proteinsUnexpected roleFunction experimentsGolgiEarly stepsProtein 1UNCNeuronal functionProtein
2021
Overlapping roles of JIP3 and JIP4 in promoting axonal transport of lysosomes in human iPSC-derived neurons
Gowrishankar S, Lyons L, Rafiq NM, Roczniak-Ferguson A, De Camilli P, Ferguson SM. Overlapping roles of JIP3 and JIP4 in promoting axonal transport of lysosomes in human iPSC-derived neurons. Molecular Biology Of The Cell 2021, 32: 1094-1103. PMID: 33788575, PMCID: PMC8351540, DOI: 10.1091/mbc.e20-06-0382.Peer-Reviewed Original ResearchConceptsAxonal transportAlzheimer's disease-related amyloid precursor proteinAmyloidogenic APP processingAmyloid precursor proteinDependence of neuronsHuman iPSCNeuronal cell biologyAPP processingAxonal lysosomesNeuronsLoss of JIP3Lysosome abundanceMovement of lysosomesPrecursor proteinCellular modelCritical regulatorStem cellsPluripotent stem cellsAβ42 peptideIPSCsLysosome transportLysosomesOverlapping rolePathologyCooperative function of synaptophysin and synapsin in the generation of synaptic vesicle-like clusters in non-neuronal cells
Park D, Wu Y, Lee SE, Kim G, Jeong S, Milovanovic D, De Camilli P, Chang S. Cooperative function of synaptophysin and synapsin in the generation of synaptic vesicle-like clusters in non-neuronal cells. Nature Communications 2021, 12: 263. PMID: 33431828, PMCID: PMC7801664, DOI: 10.1038/s41467-020-20462-z.Peer-Reviewed Original ResearchConceptsNon-neuronal cellsSV clustersSynaptic vesiclesSmall synaptic-like microvesiclesSV membrane proteinsSynaptic-like microvesiclesSV proteinsDiffuse cytosolic distributionMembrane proteinsReconstitution systemCytosolic distributionCooperative functionSuch vesiclesMechanistic insightsLiquid-like propertiesPowerful modelPhysiological formationProteinSynapsinVesiclesCellsSynaptic transmissionAssembly of structuresDefining featureLiquid condensate
2017
Contacts between the endoplasmic reticulum and other membranes in neurons
Wu Y, Whiteus C, Xu CS, Hayworth KJ, Weinberg RJ, Hess HF, De Camilli P. Contacts between the endoplasmic reticulum and other membranes in neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e4859-e4867. PMID: 28559323, PMCID: PMC5474793, DOI: 10.1073/pnas.1701078114.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumER–plasma membrane contactsER-PM contactsMembrane contactSmaller focal contactsRegulation of CaInterorganelle communicationOrganelle biogenesisDifferent neuronal compartmentsCell physiologyIntracellular membranesFocal contactsMultivesicular bodiesER contactsIntracellular organellesER cisternaeLipid homeostasisBiochemical studiesTubulovesicular structuresMembrane appositionNeuronal compartmentsImportant functionsMitochondriaReticulumMembrane
2004
Impaired PtdIns(4,5)P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking
Paolo G, Moskowitz HS, Gipson K, Wenk MR, Voronov S, Obayashi M, Flavell R, Fitzsimonds RM, Ryan TA, Camilli P. Impaired PtdIns(4,5)P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking. Nature 2004, 431: 415-422. PMID: 15386003, DOI: 10.1038/nature02896.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsBiological TransportCells, CulturedClathrinElectric ConductivityEndocytosisExocytosisGene DeletionKineticsMiceMice, KnockoutNeuronsPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositol PhosphatesPhosphotransferases (Alcohol Group Acceptor)Presynaptic TerminalsSynaptic TransmissionSynaptic VesiclesConceptsClathrin coat dynamicsSynaptic vesicle cycleSynaptic vesicle exocytosisSynaptic vesicle traffickingSecond messenger moleculesEarly postnatal lethalityEndocytic intermediatesVesicle traffickingMembrane proteinsVesicle cycleVesicle exocytosisPostnatal lethalityCell regulationRecycling kineticsMessenger moleculesBiochemical studiesSynaptic defectsDirect interactionImportant functionsCritical roleMultiple stepsReleasable poolRegulationNerve terminalsDephosphorylation
2001
Synaptojanin 1 Contributes to Maintaining the Stability of GABAergic Transmission in Primary Cultures of Cortical Neurons
Lüthi A, Di Paolo G, Cremona O, Daniell L, De Camilli P, McCormick D. Synaptojanin 1 Contributes to Maintaining the Stability of GABAergic Transmission in Primary Cultures of Cortical Neurons. Journal Of Neuroscience 2001, 21: 9101-9111. PMID: 11717343, PMCID: PMC6763888, DOI: 10.1523/jneurosci.21-23-09101.2001.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnimals, NewbornCells, CulturedCerebral CortexElectric StimulationExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsGABA AntagonistsGamma-Aminobutyric AcidMiceNerve Tissue ProteinsNeural InhibitionNeuronsPatch-Clamp TechniquesPhosphatidylinositolsPhosphoric Monoester HydrolasesSodium Channel BlockersSynapsesSynaptic TransmissionSynaptic VesiclesConceptsPaired-pulse depressionHalf-maximal depressionSteady-state depressionSynaptic depressionWhole-cell patch-clamp recordingsSlow depressionInhibitory synaptic responsesPaired-pulse protocolPrimary cortical culturesHigh-frequency stimulationPatch-clamp recordingsBi-exponential time courseUnitary IPSCsGABA releaseGABAergic transmissionCortical culturesPostsynaptic responsesCortical neuronsInhibitory synapsesSynaptic responsesSynaptojanin 1Presynaptic stimulationInhibitory neuronsRelease probabilityStimulation frequencyChronic Blockade of Glutamate Receptors Enhances Presynaptic Release and Downregulates the Interaction between Synaptophysin-Synaptobrevin–Vesicle-Associated Membrane Protein 2
Bacci A, Coco S, Pravettoni E, Schenk U, Armano S, Frassoni C, Verderio C, De Camilli P, Matteoli M. Chronic Blockade of Glutamate Receptors Enhances Presynaptic Release and Downregulates the Interaction between Synaptophysin-Synaptobrevin–Vesicle-Associated Membrane Protein 2. Journal Of Neuroscience 2001, 21: 6588-6596. PMID: 11517248, PMCID: PMC6763110, DOI: 10.1523/jneurosci.21-17-06588.2001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedDown-RegulationEndocytosisExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsExocytosisHippocampusMacromolecular SubstancesMembrane ProteinsNeuronsPatch-Clamp TechniquesPresynaptic TerminalsProtein BindingRatsReceptors, GlutamateReceptors, N-Methyl-D-AspartateR-SNARE ProteinsSynaptic TransmissionSynaptic VesiclesSynaptophysinTetrodotoxinConceptsGlutamate receptorsSynapse formationSynaptic vesicle recyclingMiniature EPSC frequencyGlutamate receptor blockersGlutamatergic nerve terminalsNumber of synapsesUptake of antibodiesVesicle recyclingChronic blockadeReceptor blockersEPSC frequencyPresynaptic releaseNerve terminalsHippocampal neuronsPresynaptic functionPostsynaptic functionChronic exposureChronic presenceInterneuronal signalingNeuronal culturesNeuronal circuitsMembrane protein 2Intracellular perfusionPrimary cultures
2000
Nobel Celebrates the Neurosciences Modulatory Signaling in the Brain
De Camilli P, Carew T. Nobel Celebrates the Neurosciences Modulatory Signaling in the Brain. Cell 2000, 103: 829-834. PMID: 11136967, DOI: 10.1016/s0092-8674(00)00185-9.Peer-Reviewed Original ResearchSynaptic Autoimmunity and the Salk Factor
Solimena M, De Camilli P. Synaptic Autoimmunity and the Salk Factor. Neuron 2000, 28: 309-316. PMID: 11144336, DOI: 10.1016/s0896-6273(00)00105-7.Peer-Reviewed Original Research
1999
Essential Role of Phosphoinositide Metabolism in Synaptic Vesicle Recycling
Cremona O, Di Paolo G, Wenk M, Lüthi A, Kim W, Takei K, Daniell L, Nemoto Y, Shears S, Flavell R, McCormick D, De Camilli P. Essential Role of Phosphoinositide Metabolism in Synaptic Vesicle Recycling. Cell 1999, 99: 179-188. PMID: 10535736, DOI: 10.1016/s0092-8674(00)81649-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell-Free SystemCerebral CortexCoated Pits, Cell-MembraneEndocytosisEnzyme InhibitorsExonsHippocampusIn Vitro TechniquesMembrane PotentialsMiceMice, KnockoutMicroscopy, ElectronNerve EndingsNerve Tissue ProteinsNeuronsPhosphatidylinositolsPhosphoric Monoester HydrolasesSynaptic VesiclesAP-2 Recruitment to Synaptotagmin Stimulated by Tyrosine-Based Endocytic Motifs
Haucke V, De Camilli P. AP-2 Recruitment to Synaptotagmin Stimulated by Tyrosine-Based Endocytic Motifs. Science 1999, 285: 1268-1271. PMID: 10455054, DOI: 10.1126/science.285.5431.1268.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex alpha SubunitsAdaptor Proteins, Vesicular TransportAnimalsBinding SitesCalcium-Binding ProteinsCattleCell MembraneCHO CellsClathrinCoated Pits, Cell-MembraneCricetinaeEndocytosisMembrane GlycoproteinsMembrane ProteinsNerve Tissue ProteinsNeuronsOligopeptidesPhospholipase DProtein BindingRatsRecombinant Fusion ProteinsSynaptic MembranesSynaptotagminsTyrosineConceptsAP-2 recruitmentEndocytic motifAP-2Cargo proteinsPlasma membraneTyrosine-based endocytic motifClathrin adaptor protein AP-2Adaptor protein AP-2Nucleation of clathrinNon-neuronal cellsProtein synaptotagminDocking siteSynaptotagminClathrinMotifProteinRecruitmentMembraneEndocytosisTyrosineBindingCellsPeptidesTetanus Toxin Blocks the Exocytosis of Synaptic Vesicles Clustered at Synapses But Not of Synaptic Vesicles in Isolated Axons
Verderio C, Coco S, Bacci A, Rossetto O, De Camilli P, Montecucco C, Matteoli M. Tetanus Toxin Blocks the Exocytosis of Synaptic Vesicles Clustered at Synapses But Not of Synaptic Vesicles in Isolated Axons. Journal Of Neuroscience 1999, 19: 6723-6732. PMID: 10436029, PMCID: PMC6782867, DOI: 10.1523/jneurosci.19-16-06723.1999.Peer-Reviewed Original Research
1998
Calcium Dependence of Synaptic Vesicle Recycling Before and After Synaptogenesis
Coco S, Verderio C, De Camilli P, Matteoli M. Calcium Dependence of Synaptic Vesicle Recycling Before and After Synaptogenesis. Journal Of Neurochemistry 1998, 71: 1987-1992. PMID: 9798923, DOI: 10.1046/j.1471-4159.1998.71051987.x.Peer-Reviewed Original ResearchConceptsSynaptic contactsCalcium concentrationSynaptic vesicle exocytosisFormation of synapsesSynaptic vesicle recyclingVesicle recyclingHippocampal neuronsIntracellular calciumVesicle exocytosisImmunocytochemical assayNeurotransmitter releaseDifferent calcium concentrationsLow calcium concentrationsSynaptic vesiclesCalcium dependenceHigh calcium concentrationsSynaptogenesisNeuronsCalciumRelease componentCalcium sensorEndocytotic recyclingExocytosis
1997
Neuronal and glial cell biology
De Camilli P, Mirsky R. Neuronal and glial cell biology. Current Opinion In Neurobiology 1997, 7: 595-597. PMID: 9384545, DOI: 10.1016/s0959-4388(97)80077-3.Peer-Reviewed Original Research
1996
Molecular mechanisms in synaptic vesicle recycling
Bauerfeind R, Galli T, De Camilli P. Molecular mechanisms in synaptic vesicle recycling. Brain Cell Biology 1996, 25: 701-715. PMID: 9023719, DOI: 10.1007/bf02284836.Peer-Reviewed Original Research
1994
Synaptic targeting of rabphilin-3A, a synaptic vesicle Ca2+/phospholipid-binding protein, depends on rab3A/3C
Li C, Takei K, Geppert M, Daniell L, Stenius K, Chapman E, Jahn R, De Camilli P, Südhof T. Synaptic targeting of rabphilin-3A, a synaptic vesicle Ca2+/phospholipid-binding protein, depends on rab3A/3C. Neuron 1994, 13: 885-898. PMID: 7946335, DOI: 10.1016/0896-6273(94)90254-2.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsBase SequenceBiological EvolutionBrain ChemistryConserved SequenceDNA, ComplementaryFluorescent Antibody TechniqueGlutathione TransferaseGTP-Binding ProteinsMiceMice, Mutant StrainsMicroscopy, ImmunoelectronMolecular Sequence DataNerve Tissue ProteinsNeuronsRab GTP-Binding ProteinsRab3 GTP-Binding ProteinsRatsRecombinant Fusion ProteinsVesicular Transport ProteinsConceptsGTP-dependent mannerSynaptic vesicle membraneRabphilin-3AVesicle membraneLow molecular weight GTPPeripheral membrane proteinsSynaptic vesiclesSynaptic vesicle dockingRab3A-deficient miceSynaptic vesicle proteinsMembrane recruitmentVesicle dockingPutative functionsMembrane proteinsWeight GTPVesicle proteinsN-terminusSynaptic targetingRab3CRab3AProteinVesiclesMembraneSynaptic patternsNormal levelsA role for synaptic vesicles in non‐neuronal cells: clues from pancreatic β cells and from chromaffin cells
Thomas‐Reetz A, De Camilli P. A role for synaptic vesicles in non‐neuronal cells: clues from pancreatic β cells and from chromaffin cells. The FASEB Journal 1994, 8: 209-216. PMID: 7907072, DOI: 10.1096/fasebj.8.2.7907072.Peer-Reviewed Original ResearchConceptsSynaptic-like microvesiclesSynaptic vesiclesAbundant synaptic vesicle proteinsVesicular carriersPancreatic beta cellsSynaptic vesicle proteinsVesicular trafficNon-neuronal cellsRecycling compartmentMembrane proteinsRecycling pathwayVesicle proteinsPancreatic β-cellsPeptide-secreting endocrine cellsMolecular mechanismsSpecialized subcompartmentBeta cellsPC12 cellsMembrane compositionVesiclesCell linesΒ-cellsOrganellesNeurotransmitter releaseNeurotransmitter-like substances
1993
Traffic of synaptic vesicle proteins in polarized and nonpolarized cells
Cameron P, Mundigl O, De Camilli P. Traffic of synaptic vesicle proteins in polarized and nonpolarized cells. Journal Of Cell Science. Supplement 1993, 1993: 93-100. PMID: 8144709, DOI: 10.1242/jcs.1993.supplement_17.14.Peer-Reviewed Original ResearchConceptsSV proteinsSynaptic vesiclesSecretory organellesSpecialized secretory organellesSynaptic-like microvesiclesExo-endocytotic recyclingSynaptic vesicle proteinsNon-peptide hormonesEndosomal intermediatesEndocrine cellsNeuronal polarityNonpolarized cellsRecycling pathwayRegulated secretionVesicle proteinsTypical synaptic vesiclesFunctional similarityLarge dense-core vesiclesDense-core vesiclesNeuronal counterpartsVesicular carriersProtein synaptophysinVesicle storesMature neuronsProteinSpotlight on a neuronal enzyme
Solimena M, De Camilli P. Spotlight on a neuronal enzyme. Nature 1993, 366: 15-17. PMID: 8232529, DOI: 10.1038/366015a0.Peer-Reviewed Original Research