2024
Parkinsonism 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 ResearchMeSH KeywordsAnimalsDopaminergic NeuronsHumansInduced Pluripotent Stem CellsMiceMutationNerve Tissue ProteinsParkinson DiseaseParkinsonian DisordersPhosphoric Monoester HydrolasesConceptsSynaptojanin 1Endocytic factorsDA neuronsCilia-mediated signalingNerve terminalsIPSC-derived dopaminergic neuronsUbiquitin chainsUbiquitinated proteinsCiliary baseCilia lengthNeurological defectsDopaminergic neuronsProtein dynamicsDomain mutationsAssembly stateIsogenic controlsNeuronsAbnormal accumulationMutationsMiceFocal concentrationParkinsonPI(4UbiquitinEndocytosis
2017
Parkinson Sac Domain Mutation in Synaptojanin 1 Impairs Clathrin Uncoating at Synapses and Triggers Dystrophic Changes in Dopaminergic Axons
Cao M, Wu Y, Ashrafi G, McCartney AJ, Wheeler H, Bushong EA, Boassa D, Ellisman MH, Ryan TA, De Camilli P. Parkinson Sac Domain Mutation in Synaptojanin 1 Impairs Clathrin Uncoating at Synapses and Triggers Dystrophic Changes in Dopaminergic Axons. Neuron 2017, 93: 882-896.e5. PMID: 28231468, PMCID: PMC5340420, DOI: 10.1016/j.neuron.2017.01.019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsClathrinDopamineEndocytosisHumansMice, TransgenicMutationParkinson DiseaseParkinsonian DisordersPhosphoric Monoester HydrolasesSynapsesConceptsDopaminergic axonsEarly-onset parkinsonism patientsEndocytic dysfunctionNeurological manifestationsParkinsonism patientsDystrophic changesParkinson's diseaseDorsal striatumHuman patientsClathrin-coated intermediatesParkin levelsHomozygous mutationMutant brainsSynaptojanin 1Domain mutationsTerminal changesPatientsStriking accumulationAxonsDiseaseMiceSynapsesSynaptic vesicle endocytosisMutationsDysfunction
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 ResearchMeSH KeywordsAge of OnsetChildChild, PreschoolCohort StudiesConsanguinityDrug Resistant EpilepsyExomeFemaleHumansMaleNerve Tissue ProteinsNeurodegenerative DiseasesPedigreePhenotypePhosphoric Monoester HydrolasesConceptsProgressive 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
2015
Preface
De Matteis A, De Camilli P. Preface. Biochimica Et Biophysica Acta 2015, 1851: 697. PMID: 25701448, DOI: 10.1016/j.bbalip.2015.02.009.Peer-Reviewed Original Research
2014
Manipulation of Plasma Membrane Phosphoinositides Using Photoinduced Protein–Protein Interactions
Idevall-Hagren O, De Camilli P. Manipulation of Plasma Membrane Phosphoinositides Using Photoinduced Protein–Protein Interactions. Methods In Molecular Biology 2014, 1148: 109-128. PMID: 24718798, DOI: 10.1007/978-1-4939-0470-9_8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsArabidopsis ProteinsCatalytic DomainCell MembraneChlorocebus aethiopsCOS CellsCryptochromesHeLa CellsHumansLightMiceMolecular Sequence DataPhosphatidylinositolsPhosphoric Monoester HydrolasesPhotochemical ProcessesProtein Interaction Domains and MotifsProtein MultimerizationRecombinant Fusion ProteinsConceptsPlasma membraneCryptochrome 2Plasma membrane phosphatidylinositolProtein-protein interactionsLight-dependent conversionLipid-binding domainLive-cell imagingCritical regulatory roleMembrane lipid metabolismPhosphoinositide speciesSpatiotemporal regulationDimerization moduleCell physiologyMembrane phosphatidylinositolRegulatory roleTypes of cellsInositol phospholipidsPhosphorylated productsDimerization methodLipid metabolismMembraneCIB1DephosphorylationPhosphatidylinositolPhosphoinositide
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 frequencyPIP 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 Acid
2000
Functional Characterization of a Mammalian Sac1 and Mutants Exhibiting Substrate-specific Defects in Phosphoinositide Phosphatase Activity*
Nemoto Y, Kearns B, Wenk M, Chen H, Mori K, Alb J, De Camilli P, Bankaitis V. Functional Characterization of a Mammalian Sac1 and Mutants Exhibiting Substrate-specific Defects in Phosphoinositide Phosphatase Activity*. Journal Of Biological Chemistry 2000, 275: 34293-34305. PMID: 10887188, DOI: 10.1074/jbc.m003923200.Peer-Reviewed Original ResearchConceptsSubstrate-specific defectsIntegral membrane proteinsPhosphoinositide phosphatase activityPhosphatase activityMembrane proteinsEndoplasmic reticulumGolgi secretory functionIntegral membrane lipidEukaryotic cell physiologyPrimary sequence homologyYeast Sac1pSAC1 geneHeterologous complementationActin functionSac1 domainSac1pBisphosphate substrateMembrane phosphoinositidesPhosphatidylinositol 3Cell physiologyFunctional characterizationGene productsSequence homologyProtein activityGolgi complexFission 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 switchUncoatingEndocytosisVesiclesDirect 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 VesiclesRecruitment 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 roleOmp25Protein
1998
Role of Phosphorylation in Regulation of the Assembly of Endocytic Coat Complexes
Slepnev V, Ochoa G, Butler M, Grabs D, De Camilli P. Role of Phosphorylation in Regulation of the Assembly of Endocytic Coat Complexes. Science 1998, 281: 821-824. PMID: 9694653, DOI: 10.1126/science.281.5378.821.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex alpha SubunitsAdaptor Protein Complex beta SubunitsAdaptor Proteins, Vesicular TransportAdenosine TriphosphateAnimalsBinding SitesCarbazolesChromatography, AffinityClathrinCyclosporineDimerizationDynamin IDynaminsEndocytosisEnzyme InhibitorsGTP PhosphohydrolasesIndole AlkaloidsMembrane ProteinsNerve Tissue ProteinsPhosphoric Monoester HydrolasesRatsRecombinant Fusion ProteinsSrc Homology DomainsGeneration of Coated Intermediates of Clathrin-Mediated Endocytosis on Protein-Free Liposomes
Takei K, Haucke V, Slepnev V, Farsad K, Salazar M, Chen H, De Camilli P. Generation of Coated Intermediates of Clathrin-Mediated Endocytosis on Protein-Free Liposomes. Cell 1998, 94: 131-141. PMID: 9674434, DOI: 10.1016/s0092-8674(00)81228-3.Peer-Reviewed Original ResearchAmphiphysin I Antisense Oligonucleotides Inhibit Neurite Outgrowth in Cultured Hippocampal Neurons
Mundigl O, Ochoa G, David C, Slepnev V, Kabanov A, De Camilli P. Amphiphysin I Antisense Oligonucleotides Inhibit Neurite Outgrowth in Cultured Hippocampal Neurons. Journal Of Neuroscience 1998, 18: 93-103. PMID: 9412489, PMCID: PMC6793426, DOI: 10.1523/jneurosci.18-01-00093.1998.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCalcium-Binding ProteinsCells, CulturedDynamin IDynaminsEndocytosisGene ExpressionGTP PhosphohydrolasesHippocampusMembrane GlycoproteinsMiceNerve Tissue ProteinsNeuritesOligonucleotides, AntisensePhosphoric Monoester HydrolasesRabbitsRatsRNA, MessengerSynaptic VesiclesSynaptotagminsTubulinConceptsAmphiphysin IDynamin ICell polarityNeurite outgrowthSynaptic vesicle endocytosisPhysiological binding partnerGrowth conesClose functional linkYeast homologActin patchesActin functionVesicle endocytosisActin dynamicsProtein familyBinding partnerCell cytoskeletonAxon formationFunctional linkNeuronal differentiationWestern blot analysisCultured hippocampal neuronsHippocampal neuronsDevelopmental stagesNeuronal proteinsAmphipathic polymers
1997
Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15
Haffner C, Takei K, Chen H, Ringstad N, Hudson A, Butler M, Salcini A, Di Fiore P, De Camilli P. Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15. FEBS Letters 1997, 419: 175-180. PMID: 9428629, DOI: 10.1016/s0014-5793(97)01451-8.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsCalcium-Binding ProteinsClathrinEndocytosisHumansImmunohistochemistryIntracellular Signaling Peptides and ProteinsMolecular Sequence DataNerve EndingsNerve Tissue ProteinsPhosphoproteinsPhosphoric Monoester HydrolasesRatsSequence AlignmentSynaptic TransmissionSynaptic VesiclesConceptsSynaptojanin 1Endocytic intermediatesClathrin-coated pitsCOOH-terminal regionEH domainSpecies threeEps15Multiplicity of interactionsPutative roleClathrinNerve terminalsEndocytosisIsoformsProteinPrevious dataMotifInositolIntermediatesBindingInteractionPhenylalanineLocalizationNew evidenceDomainAmphiphysin I Is Associated with Coated Endocytic Intermediates and Undergoes Stimulation-dependent Dephosphorylation in Nerve Terminals*
Bauerfeind R, Takei K, De Camilli P. Amphiphysin I Is Associated with Coated Endocytic Intermediates and Undergoes Stimulation-dependent Dephosphorylation in Nerve Terminals*. Journal Of Biological Chemistry 1997, 272: 30984-30992. PMID: 9388246, DOI: 10.1074/jbc.272.49.30984.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcineurinDynamin IDynaminsElectrophoresis, Polyacrylamide GelEndocytosisEnzyme InhibitorsGTP PhosphohydrolasesGTP-Binding ProteinsGuanosine 5'-O-(3-Thiotriphosphate)Microscopy, ElectronMicrotubulesNerve Tissue ProteinsPhospholipase DPhosphoric Monoester HydrolasesPhosphorylationPresynaptic TerminalsRatsConceptsSrc homology 3Dynamin IAmphiphysin IEndocytic intermediatesCalcineurin-dependent dephosphorylationSynaptic vesicle endocytosisSynaptic vesicle exocytosisSynaptic vesicle recyclingClathrin-coated budsBurst of exocytosisAbundant presynaptic proteinElectron microscopy immunocytochemistryHomology 3Vesicle endocytosisVesicle exocytosisConstitutive phosphorylationVesicle recyclingRapid dephosphorylationOkadaic acidPhysiological partnersDephosphorylationBinding proteinPutative rolePresynaptic proteinsProteinThe SH3p4/Sh3p8/SH3p13 protein family: Binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain
Ringstad N, Nemoto Y, De Camilli P. The SH3p4/Sh3p8/SH3p13 protein family: Binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 8569-8574. PMID: 9238017, PMCID: PMC23017, DOI: 10.1073/pnas.94.16.8569.Peer-Reviewed Original ResearchConceptsSrc homology 3 domainSynaptic vesicle recyclingDynamin IProtein familyVesicle recyclingSH3 domain-containing proteinsDomain-containing proteinsProline-rich domainTwo-hybrid methodPhysiological binding partnerProline-rich tailRat brain libraryFurther biochemical studiesSH3 domainSynaptojaninDynamin I.Nerve terminal proteinBinding partnerTerminal proteinAmphiphysin IRelated proteinsBrain libraryMultiple tissuesBiochemical studiesProtein
1996
A 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