2024
Overlapping role of synaptophysin and synaptogyrin family proteins in determining the small size of synaptic vesicles
Park D, Fujise K, Wu Y, Luján R, Del Olmo-Cabrera S, Wesseling J, De Camilli P. Overlapping role of synaptophysin and synaptogyrin family proteins in determining the small size of synaptic vesicles. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2409605121. PMID: 38985768, PMCID: PMC11260120, DOI: 10.1073/pnas.2409605121.Peer-Reviewed Original ResearchConceptsSynaptic vesiclesFamily proteinsBiogenesis of synaptic vesiclesClusters of small vesiclesSize of synaptic vesiclesSynaptogyrin familySynaptogyrin-1Vesicle proteinsSynaptogyrinTransmembrane domainOrganismal levelSmall vesiclesProteinMild defectsVesiclesFamily membersBiogenesisSmall sizeFamilyMiceSynapsinCoexpressionAbundanceSynaptoporinMembers
2022
Multimodal imaging of synaptic vesicles with a single probe
An SJ, Stagi M, Gould TJ, Wu Y, Mlodzianoski M, Rivera-Molina F, Toomre D, Strittmatter SM, De Camilli P, Bewersdorf J, Zenisek D. Multimodal imaging of synaptic vesicles with a single probe. Cell Reports Methods 2022, 2: 100199. PMID: 35497490, PMCID: PMC9046237, DOI: 10.1016/j.crmeth.2022.100199.Peer-Reviewed Original ResearchConceptsC2 domainSynaptic vesiclesSynaptic vesicle recyclingMembrane-binding C2 domainMultiple microscopy methodsEndocytic markersMembrane recyclingVesicle functionVesicle populationsCytosolic phospholipase ACell typesPhospholipase ADetectable tagMicroscopy modalitiesModular probesMultiple microscopy techniquesVesiclesComplete understandingDomainMicroscopy methodsMultiple levelsProbeAvailable probesMicroscopy techniquesPathway
2021
Cooperative 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
2018
A liquid phase of synapsin and lipid vesicles
Milovanovic D, Wu Y, Bian X, De Camilli P. A liquid phase of synapsin and lipid vesicles. Science 2018, 361: 604-607. PMID: 29976799, PMCID: PMC6191856, DOI: 10.1126/science.aat5671.Peer-Reviewed Original ResearchConceptsSynaptic vesiclesNeurotransmitter-containing synaptic vesiclesCalmodulin-dependent protein kinase IILipid vesiclesCalcium/calmodulin-dependent protein kinase IIProtein kinase IISmall lipid vesiclesKinase IILiquid-liquid phase separationSynapsinDistinct liquid phasesVesiclesTight clusterSynapsin 1Presynaptic sitesPhosphorylationExocytosis
2008
Molecular mechanisms in endocytosis at neuronal synapses
De Camilli P. Molecular mechanisms in endocytosis at neuronal synapses. The FASEB Journal 2008, 22: 250.3-250.3. DOI: 10.1096/fasebj.22.1_supplement.250.3.Peer-Reviewed Original ResearchFunction of dynaminNeuronal synapsesPowerful model systemRole of isoformsGTPase dynaminEndocytic proteinsEndocytic recyclingPlasma membraneMolecular mechanismsSecretory systemReconstitution experimentsEndocytosisSynaptic vesiclesHigh specializationDynaminLipid membranesRelease of neurotransmittersModel systemProteinMembraneFundamental mechanismsComplementary approachesRecent advancesDephosphorylationOrganelles
2001
The Eps15 C. elegans homologue EHS-1 is implicated in synaptic vesicle recycling
Salcini A, Hilliard M, Croce A, Arbucci S, Luzzi P, Tacchetti C, Daniell L, De Camilli P, Pelicci P, Di Fiore P, Bazzicalupo P. The Eps15 C. elegans homologue EHS-1 is implicated in synaptic vesicle recycling. Nature Cell Biology 2001, 3: 755-760. PMID: 11483962, DOI: 10.1038/35087075.Peer-Reviewed Original ResearchMeSH KeywordsAldicarbAnimalsAnimals, Genetically ModifiedCaenorhabditis elegansCalcium-Binding ProteinsDynaminsFluorescent Antibody TechniqueGanglia, InvertebrateGene DeletionGenes, ReporterGTP PhosphohydrolasesInsecticidesMicroscopy, ElectronMolecular Sequence DataMovement DisordersMutationNerve Tissue ProteinsNervous SystemPhenotypePhosphoproteinsProtein TransportSequence Homology, Nucleic AcidSynaptic VesiclesTemperatureConceptsSynaptic vesicle recyclingVesicle recyclingEHS-1Protein-protein interactionsMammalian Eps15Dynamin proteinsEH domainEndocytic machineryEps15Mutant formsPermissive temperatureFunctional studiesSynaptic vesiclesDynaminUncoordinated movementsPresynaptic defectsProteinPhenotypeOrthologuesCaenorhabditisWormsGenesNematodesMachineryVesicles
2000
Dual interaction of synaptotagmin with μ2‐ and α‐adaptin facilitates clathrin‐coated pit nucleation
Haucke V, Wenk M, Chapman E, Farsad K, De Camilli P. Dual interaction of synaptotagmin with μ2‐ and α‐adaptin facilitates clathrin‐coated pit nucleation. The EMBO Journal 2000, 19: 6011-6019. PMID: 11080148, PMCID: PMC305843, DOI: 10.1093/emboj/19.22.6011.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex 1Adaptor Protein Complex 2Adaptor Protein Complex 3Adaptor Protein Complex alpha SubunitsAdaptor Protein Complex mu SubunitsAdaptor Proteins, Vesicular TransportAnimalsBinding SitesCalcium-Binding ProteinsCHO CellsClathrinCoated Pits, Cell-MembraneCricetinaeIn Vitro TechniquesLiposomesLysineMembrane GlycoproteinsMembrane ProteinsMutationNerve Tissue ProteinsPhosphoproteinsProtein SubunitsRatsSynaptic VesiclesSynaptotagminsTyrosineConceptsAP-2C2B domainEndocytic adaptor complex AP-2Endocytic clathrin-coated pitsAdaptor complex AP-2Clathrin adaptor AP-2Synaptic vesicle protein synaptotagminTyrosine-based sorting motifAdaptor AP-2Clathrin-coated pitsMajor docking siteKey physiological rolesDual interactionSorting motifClathrin coatTransferrin internalizationProtein synaptotagminDocking siteSubdomain BSynaptotagminPhysiological roleLiving cellsSynaptic vesiclesSubunitsMu2Specificity of the Binding of Synapsin I to Src Homology 3 Domains*
Onofri F, Giovedı̀ S, Kao H, Valtorta F, Borbone L, De Camilli P, Greengard P, Benfenati F. Specificity of the Binding of Synapsin I to Src Homology 3 Domains*. Journal Of Biological Chemistry 2000, 275: 29857-29867. PMID: 10899172, DOI: 10.1074/jbc.m006018200.Peer-Reviewed Original ResearchConceptsSrc homology 3 domainSH3 domainCOOH-terminal regionSynapsin ISignal transductionC-SrcSynaptic vesicle-associated phosphoproteinsMultiple SH3 domainsGTPase-activating proteinsProtein-protein interactionsMitogen-activated protein kinaseDependent protein kinase IIProtein kinase IICytoskeleton assemblyP85 subunitDistinct binding patternsHigh-affinity interactionProtein kinaseAmphiphysin IC gammaKinase IIAlpha-spectrinGrb2SH3Synaptic vesiclesTandem Arrangement of the Clathrin and AP-2 Binding Domains in Amphiphysin 1 and Disruption of Clathrin Coat Function by Amphiphysin Fragments Comprising These Sites*
Slepnev V, Ochoa G, Butler M, De Camilli P. Tandem Arrangement of the Clathrin and AP-2 Binding Domains in Amphiphysin 1 and Disruption of Clathrin Coat Function by Amphiphysin Fragments Comprising These Sites*. Journal Of Biological Chemistry 2000, 275: 17583-17589. PMID: 10748223, DOI: 10.1074/jbc.m910430199.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex alpha SubunitsAdaptor Proteins, Vesicular TransportAmino Acid SequenceAnimalsBinding SitesBinding, CompetitiveCHO CellsClathrinCricetinaeGlutathione TransferaseHumansMembrane ProteinsMolecular Sequence DataMonomeric Clathrin Assembly ProteinsMutagenesis, Site-DirectedNerve Tissue ProteinsPeptide FragmentsRecombinant Fusion ProteinsTransfectionConceptsAP-2Amphiphysin 1Coat proteinClathrin adaptor AP-2COOH-terminal SH3 domainAdaptor AP-2Chinese hamster ovary cellsCoat functionMultifunctional adaptorSH3 domainHamster ovary cellsTerminal domainBinding domainsClathrinDynaminMembrane lipidsAmphiphysinSynaptic vesiclesAmino acidsSynaptojaninOvary cellsDirect interactionProteinTertiary complexTandem arrangement
1999
The Calcineurin-Dynamin 1 Complex as a Calcium Sensor for Synaptic Vesicle Endocytosis*
Lai M, Hong J, Ruggiero A, Burnett P, Slepnev V, De Camilli P, Snyder S. The Calcineurin-Dynamin 1 Complex as a Calcium Sensor for Synaptic Vesicle Endocytosis*. Journal Of Biological Chemistry 1999, 274: 25963-25966. PMID: 10473536, DOI: 10.1074/jbc.274.37.25963.Peer-Reviewed Original ResearchConceptsCalcium sensorEndocytic coat proteinsSynaptic endocytic machinerySynaptic vesicle endocytosisSynaptic vesiclesCalcium-dependent phosphatase calcineurinEndocytic machineryVesicle endocytosisDynamin 1Phosphatase calcineurinCoat proteinCalcium-dependent formationCalcium-sensing mechanismPhysical associationEndocytosisVesiclesCalcium-dependent processesClathrinSynaptotagminComplexesExocytosisCalcineurinMachineryProteinTetanus 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 ResearchRecruitment of an alternatively spliced form of synaptojanin 2 to mitochondria by the interaction with the PDZ domain of a mitochondrial outer membrane protein
Nemoto Y, De Camilli P. Recruitment of an alternatively spliced form of synaptojanin 2 to mitochondria by the interaction with the PDZ domain of a mitochondrial outer membrane protein. The EMBO Journal 1999, 18: 2991-3006. PMID: 10357812, PMCID: PMC1171381, DOI: 10.1093/emboj/18.11.2991.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAmino Acid SequenceAnimalsBase SequenceBinding SitesCarrier ProteinsCHO CellsCloning, MolecularCricetinaeCytoplasmExonsIntracellular MembranesIsoenzymesMembrane ProteinsMitochondriaMolecular Sequence DataMutationNerve Tissue ProteinsPhosphoric Monoester HydrolasesProtein BindingRatsRecombinant Fusion ProteinsRNA, MessengerYeastsConceptsMitochondrial outer membrane proteinMitochondrial outer membraneOuter membrane proteinsPDZ domainMembrane proteinsSynaptojanin 2Outer membraneNovel mitochondrial outer membrane proteinC-terminal transmembrane regionSingle PDZ domainPerinuclear clusteringTransmembrane regionSynaptojanin 1C-terminusExon sequencesSpliced formsEnforced expressionUnique motifModulation of inositolIntracellular distributionSynaptic vesiclesMitochondriaPutative roleOmp25ProteinFunctional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis
Takei K, Slepnev V, Haucke V, De Camilli P. Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis. Nature Cell Biology 1999, 1: 33-39. PMID: 10559861, DOI: 10.1038/9004.Peer-Reviewed Original ResearchConceptsDynamin 1Functional partnershipCell-free systemAmphiphysin 1Clathrin coatDynaminAmphiphysinRing-like structurePresence of GTPSynaptic vesiclesEndocytosisNarrow tubulesLipid bilayersMorphological evidenceBilayer curvatureVesiclesSpherical liposomesPotential functionClathrinGTPDirect morphological evidenceProteinAssembles
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
Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity
Onofri F, Giovedì S, Vaccaro P, Czernik A, Valtorta F, De Camilli P, Greengard P, Benfenati F. Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 12168-12173. PMID: 9342381, PMCID: PMC23739, DOI: 10.1073/pnas.94.22.12168.Peer-Reviewed Original ResearchConceptsTyrosine kinase activityC-SrcKinase activitySynapsin ISrc homology 3 domainNonreceptor tyrosine kinase c-SrcSynaptic vesicle-associated phosphoproteinsTyrosine kinase c-SrcSynaptic vesiclesC-Src SH3 domainKinase c-SrcEndogenous tyrosine kinase activityTotal cellular poolStoichiometric phosphorylationSynaptic vesicle preparationsCoprecipitation assaysSignal transductionProtein speciesCellular poolRegulatory sitesBinding proteinVesicle preparationsDetergent extractsSeveralfold stimulationAffinity chromatographySynaptic vesicle endocytosis
Cremona O, De Camilli P. Synaptic vesicle endocytosis. Current Opinion In Neurobiology 1997, 7: 323-330. PMID: 9232811, DOI: 10.1016/s0959-4388(97)80059-1.Peer-Reviewed Original ResearchRecycling of Synaptic Vesicles
Bauerfeind R, David C, Grabs D, McPherson P, Nemoto Y, Slepnev V, Takei K, De Camilli P. Recycling of Synaptic Vesicles. Advances In Pharmacology 1997, 42: 253-257. PMID: 9327892, DOI: 10.1016/s1054-3589(08)60741-3.Peer-Reviewed Original ResearchConceptsSynaptic vesicle endocytosisSynaptic vesicle recyclingVesicle endocytosisVesicle recyclingSynaptic vesiclesPlasma membraneClathrin adaptor complex AP2Vesicular transport stepsClathrin-coated vesiclesClathrin-coated pitsMicrotubule-binding proteinSynaptic vesicle cycleRole of proteinsCell surface receptorsRole of lipidsClathrin coatRestrictive temperatureEarly endosomesGuanosine triphosphataseRecycling pathwayVesicle cycleDynaminTransport stepsEndocytosisSurface receptors
1996
Alzheimer Amyloid Protein Precursor Is Localized in Nerve Terminal Preparations to Rab5-containing Vesicular Organelles Distinct from Those Implicated in the Synaptic Vesicle Pathway*
Ikin A, Annaert W, Takei K, De Camilli P, Jahn R, Greengard P, Buxbaum J. Alzheimer Amyloid Protein Precursor Is Localized in Nerve Terminal Preparations to Rab5-containing Vesicular Organelles Distinct from Those Implicated in the Synaptic Vesicle Pathway*. Journal Of Biological Chemistry 1996, 271: 31783-31786. PMID: 8943215, DOI: 10.1074/jbc.271.50.31783.Peer-Reviewed Original ResearchConceptsAmyloid protein precursorSmall synaptic vesiclesSynaptic vesiclesVesicular organellesProtein precursorSynaptic vesicle recycling pathwayNerve terminal preparationsSynaptic vesicle pathwayVesicle recycling pathwayAlzheimer amyloid protein precursorRecycling pathwayVesicle pathwayOrganellesVesiclesImmunoisolatesPathwayHomogeneous populationRab5Nerve terminalsHigh levelsDistinctPrecursorsSubstantial numberBilamellar vesiclesA presynaptic inositol-5-phosphatase
McPherson P, Garcia E, Slepnev V, David C, Zhang X, Grabs D, Sossini W, Bauerfeind R, Nemoto Y, De Camilli P. A presynaptic inositol-5-phosphatase. Nature 1996, 379: 353-357. PMID: 8552192, DOI: 10.1038/379353a0.Peer-Reviewed Original ResearchConceptsSH3 domainAmino-terminal domainSynaptic vesicle recyclingRelative molecular massPutative functionsNerve terminal proteinSynaptojaninTerminal proteinVesicle recyclingMajor brain proteinsCarboxy terminusTermination sitesMolecular massOculocerebrorenal syndromeSynaptic vesiclesPresynaptic proteinsDynaminPhosphoinositide metabolismProteinBrain proteinsPhospholipid metabolismMetabolismGrb2DomainGenes
1995
Molecular mechanisms in synaptic vesicle recycling
De Camilli P. Molecular mechanisms in synaptic vesicle recycling. FEBS Letters 1995, 369: 3-12. PMID: 7641879, DOI: 10.1016/0014-5793(95)00739-v.Peer-Reviewed Original ResearchConceptsSynaptic vesicle recyclingVesicle recyclingSynaptic vesiclesMolecular mechanismsPowerful experimental modelVesicular trafficVesicle reformationNon-peptide neurotransmittersSecretory organellesRecycling pathwayHigh specializationVesiclesSpecialized formExocytosisRecent studiesNerve terminalsOrganellesMechanismRecyclingAbundanceCurrent informationPathwayUnique properties