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 ResearchMeSH KeywordsAnimalsFibroblastsMembrane ProteinsMiceMice, KnockoutNerve Tissue ProteinsRatsSynapsinsSynaptic VesiclesSynaptogyrinsSynaptophysinConceptsSynaptic vesiclesFamily proteinsBiogenesis of synaptic vesiclesClusters of small vesiclesSize of synaptic vesiclesSynaptogyrin familySynaptogyrin-1Vesicle proteinsSynaptogyrinTransmembrane domainOrganismal levelSmall vesiclesProteinMild defectsVesiclesFamily membersBiogenesisSmall sizeFamilyMiceSynapsinCoexpressionAbundanceSynaptoporinMembersParkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons
Rafiq N, Fujise K, Rosenfeld M, Xu P, De Camilli P. Parkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2318943121. PMID: 38635628, PMCID: PMC11047088, DOI: 10.1073/pnas.2318943121.Peer-Reviewed Original ResearchConceptsSynaptojanin 1Endocytic factorsDA neuronsCilia-mediated signalingNerve terminalsIPSC-derived dopaminergic neuronsUbiquitin chainsUbiquitinated proteinsCiliary baseCilia lengthNeurological defectsDopaminergic neuronsProtein dynamicsDomain mutationsAssembly stateIsogenic controlsNeuronsAbnormal accumulationMutationsMiceFocal concentrationParkinsonPI(4UbiquitinEndocytosis
2022
JIP3 links lysosome transport to regulation of multiple components of the axonal cytoskeleton
Rafiq N, Lyons L, Gowrishankar S, De Camilli P, Ferguson S. JIP3 links lysosome transport to regulation of multiple components of the axonal cytoskeleton. Communications Biology 2022, 5: 5. PMID: 35013510, PMCID: PMC8748971, DOI: 10.1038/s42003-021-02945-x.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAxonal TransportAxonsBiological TransportCytoskeletonHumansLysosomesNerve Tissue Proteins
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 rolePathology
2016
Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline
Hardies K, Cai Y, Jardel C, Jansen AC, Cao M, May P, Djémié T, Le Camus C, Keymolen K, Deconinck T, Bhambhani V, Long C, Sajan SA, Helbig KL, Consortium A, Suls A, Balling R, Helbig I, De Jonghe P, Depienne C, De Camilli P, Weckhuysen S, Afawi Z, Baulac S, Barisic N, Caglayan H, Craiu D, De Kovel C, Lopez R, Guerrini R, Hjalgrim H, Lerche H, Jahn J, Klein K, Koeleman B, Leguern E, Lemke J, Marini C, Muhle H, Rosenow F, Serratosa J, Štěrbová K, Møller R, Palotie A, Striano P, Weber Y, Zara F. Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline. Brain 2016, 139: 2420-2430. PMID: 27435091, PMCID: PMC4995362, DOI: 10.1093/brain/aww180.Peer-Reviewed Original ResearchConceptsProgressive neurological declineEarly-onset refractory seizuresHomozygous missense variantEarly-onset parkinsonismRefractory seizuresNeurological declineOnset parkinsonismNeurodegenerative disease courseAdditional pathogenic variantsMissense variantsDifferent neurological diseasesHomozygous nonsense variantDual phosphatase activityDisease courseRefractory epilepsyTau pathologyClinical spectrumIntractable epilepsySevere epilepsySeizure pathophysiologySynaptic dysregulationLarge cohortSingle patientNeurological diseasesEpilepsy
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 frequencyGeneration of high curvature membranes mediated by direct endophilin bilayer interactions
Farsad K, Ringstad N, Takei K, Floyd S, Rose K, De Camilli P. Generation of high curvature membranes mediated by direct endophilin bilayer interactions. Journal Of Cell Biology 2001, 155: 193-200. PMID: 11604418, PMCID: PMC2198845, DOI: 10.1083/jcb.200107075.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsBiological TransportCarrier ProteinsCell MembraneCell SizeDynaminsGolgi ApparatusGTP PhosphohydrolasesHumansLipid BilayersMacromolecular SubstancesMolecular Sequence DataNerve Tissue ProteinsPhylogenyProtein Structure, TertiaryRatsSequence Homology, Amino AcidSynaptic VesiclesConceptsEndophilin-1Lipid bilayersMembrane-trafficking eventsAmino acid stretchHigh-curvature membranesNH2-terminal regionCell-free systemEndophilin BEndophilin functionGTPase dynaminDynamin ringsVesicle buddingEndophilinEndocytic vesiclesGolgi complexNarrow tubulesMembrane deformationCorresponding regionProteinTransferase activityAcyl transferase activityBilayer interactionsNew insightsLipid tubulesPotential rolePIP Kinase Iγ Is the Major PI(4,5)P2 Synthesizing Enzyme at the Synapse
Wenk M, Pellegrini L, Klenchin V, Di Paolo G, Chang S, Daniell L, Arioka M, Martin T, De Camilli P. PIP Kinase Iγ Is the Major PI(4,5)P2 Synthesizing Enzyme at the Synapse. Neuron 2001, 32: 79-88. PMID: 11604140, DOI: 10.1016/s0896-6273(01)00456-1.Peer-Reviewed Original ResearchConceptsSynaptojanin 1Clathrin-coated intermediatesPolyphosphoinositide phosphatase synaptojanin-1Coat recruitmentActin functionClathrin coatPositive regulatorEndocytic zonesPIPKIgammaSynthesizing enzymesRecruitmentIgammaSynapseDephosphorylationEndocytosisMajor brainElevated levelsRegulatorProteinActinEnzymeMembraneIdentification and Characterization of a Synaptojanin 2 Splice Isoform Predominantly Expressed in Nerve Terminals*
Nemoto Y, Wenk M, Watanabe M, Daniell L, Murakami T, Ringstad N, Yamada H, Takei K, De Camilli P. Identification and Characterization of a Synaptojanin 2 Splice Isoform Predominantly Expressed in Nerve Terminals*. Journal Of Biological Chemistry 2001, 276: 41133-41142. PMID: 11498538, DOI: 10.1074/jbc.m106404200.Peer-Reviewed Original ResearchAmino Acid SequenceAnimalsBase SequenceChromatography, AffinityCloning, MolecularDNA PrimersGTP PhosphohydrolasesHumansMolecular Sequence DataMutagenesis, Site-DirectedNerve EndingsNerve Tissue ProteinsPhosphoric Monoester HydrolasesProtein IsoformsRac1 GTP-Binding ProteinRatsRNA SplicingSequence Homology, Amino AcidThe 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 defectsProteinPhenotypeOrthologuesCaenorhabditisWormsGenesNematodesMachineryVesiclesAutoimmunity to βIV spectrin in paraneoplastic lower motor neuron syndrome
Berghs S, Ferracci F, Maksimova E, Gleason S, Leszczynski N, Butler M, De Camilli P, Solimena M. Autoimmunity to βIV spectrin in paraneoplastic lower motor neuron syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 6945-6950. PMID: 11391009, PMCID: PMC34458, DOI: 10.1073/pnas.121170798.Peer-Reviewed Original ResearchConceptsLower motor neuron syndromeMotor neuron syndromeParaneoplastic neurological disordersAxons of motoneuronsSevere neurological diseaseAxon initial segmentNodes of RanvierAutoimmune pathogenesisAutoimmune targetNeurological symptomsBreast cancerPartial improvementNeurological diseasesAffected neuronsNeurological disordersSyndromeAutoantibodiesCancer removalCancer cellsBetaIV spectrinAutoimmunityMajor targetSurface epitopesPathogenesisAxons
2000
Amphiphysin 1 Binds the Cyclin-dependent Kinase (cdk) 5 Regulatory Subunit p35 and Is Phosphorylated by cdk5 and cdc2*
Floyd S, Porro E, Slepnev V, Ochoa G, Tsai L, De Camilli P. Amphiphysin 1 Binds the Cyclin-dependent Kinase (cdk) 5 Regulatory Subunit p35 and Is Phosphorylated by cdk5 and cdc2*. Journal Of Biological Chemistry 2000, 276: 8104-8110. PMID: 11113134, DOI: 10.1074/jbc.m008932200.Peer-Reviewed Original ResearchConceptsAmphiphysin 1Kinase familyCyclin-dependent protein kinase familyCyclin-dependent kinase familyProtein kinase familySynaptic vesicle endocytosisB kinase complexNeurite outgrowthSubunit p35Cyclin-dependent kinase 5NH2-terminal regionMitotic phosphorylationYeast homologueImportant physiological roleSerine 272Vesicle endocytosisActin cytoskeletonKinase complexRegulatory subunit p35Actin dynamicsPeripheral lamellipodiaDifferentiated cellsKinase 5AmphiphysinPhysiological roleDual 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 vesiclesSubunitsMu2Synaptic 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 ResearchFission and Uncoating of Synaptic Clathrin-Coated Vesicles Are Perturbed by Disruption of Interactions with the SH3 Domain of Endophilin
Gad H, Ringstad N, Löw P, Kjaerulff O, Gustafsson J, Wenk M, Di Paolo G, Nemoto Y, Crum J, Ellisman M, De Camilli P, Shupliakov O, Brodin L. Fission and Uncoating of Synaptic Clathrin-Coated Vesicles Are Perturbed by Disruption of Interactions with the SH3 Domain of Endophilin. Neuron 2000, 27: 301-312. PMID: 10985350, DOI: 10.1016/s0896-6273(00)00038-6.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBinding, CompetitiveCarrier ProteinsClathrinCloning, MolecularCoated Pits, Cell-MembraneDynaminsGTP PhosphohydrolasesLampreysMicroinjectionsMolecular Sequence DataNerve Tissue ProteinsPeptide FragmentsPhosphoric Monoester HydrolasesSequence Homology, Amino AcidSrc Homology DomainsSynaptic VesiclesConceptsProline-rich domainSynaptic vesicle endocytosisSH3 domainVesicle endocytosisEndophilin's SH3 domainClathrin coat formationClathrin-coated vesiclesClathrin-coated pitsDisruption of interactionsEndocytic intermediatesProteinprotein interactionsCoat formationEndophilinMolecular switchUncoatingEndocytosisVesiclesTandem 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 arrangementDirect interaction of the 170 kDa isoform of synaptojanin 1 with clathrin and with the clathrin adaptor AP-2
Haffner C, Di Paolo G, Rosenthal J, De Camilli P. Direct interaction of the 170 kDa isoform of synaptojanin 1 with clathrin and with the clathrin adaptor AP-2. Current Biology 2000, 10: 471-474. PMID: 10801423, DOI: 10.1016/s0960-9822(00)00446-2.Peer-Reviewed Original ResearchConceptsClathrin adaptor AP-2Adaptor AP-2AP-2Synaptojanin 1Unique carboxy-terminal regionClathrin coat dynamicsAlpha-adaptin subunitCarboxy-terminal domainCarboxy-terminal extensionAmino-terminal domainSynaptic vesicle recyclingCarboxy-terminal regionBinding of clathrinReceptor-mediated endocytosisChinese hamster ovary cellsActin functionPolyphosphoinositide phosphataseEar domainClathrin coatHamster ovary cellsVesicle recyclingVariety of tissuesTransferrin uptakePleiotropic rolesClathrin
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