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 ResearchConceptsSynaptojanin 1Endocytic factorsDA neuronsCilia-mediated signalingNerve terminalsIPSC-derived dopaminergic neuronsUbiquitin chainsUbiquitinated proteinsCiliary baseCilia lengthNeurological defectsDopaminergic neuronsProtein dynamicsDomain mutationsAssembly stateIsogenic controlsNeuronsAbnormal accumulationMutationsMiceFocal concentrationParkinsonPI(4UbiquitinEndocytosis
2023
Mutations in Parkinsonism-linked endocytic proteins synaptojanin1 and auxilin have synergistic effects on dopaminergic axonal pathology
Ng X, Wu Y, Lin Y, Yaqoob S, Greene L, De Camilli P, Cao M. Mutations in Parkinsonism-linked endocytic proteins synaptojanin1 and auxilin have synergistic effects on dopaminergic axonal pathology. Npj Parkinson's Disease 2023, 9: 26. PMID: 36792618, PMCID: PMC9932162, DOI: 10.1038/s41531-023-00465-5.Peer-Reviewed Original ResearchParkinson's diseaseMutant miceStriatal nerve terminalsSingle mutant miceDouble mutant miceDAergic markersDAergic terminalsAtypical parkinsonismDAergic neuronsStriatal interneuronsNeurological manifestationsAxonal pathologyDopaminergic inputNerve terminalsSynaptojanin 1Dystrophic changesPD pathogenesisKnockout miceRisk proteinsSynaptic defectsNeurodegenerative disordersParkinsonismMiceAdaptive changesDisease
2022
Presynaptic autophagy is coupled to the synaptic vesicle cycle via ATG-9
Yang S, Park D, Manning L, Hill SE, Cao M, Xuan Z, Gonzalez I, Dong Y, Clark B, Shao L, Okeke I, Almoril-Porras A, Bai J, De Camilli P, Colón-Ramos DA. Presynaptic autophagy is coupled to the synaptic vesicle cycle via ATG-9. Neuron 2022, 110: 824-840.e10. PMID: 35065714, PMCID: PMC9017068, DOI: 10.1016/j.neuron.2021.12.031.Peer-Reviewed Original ResearchConceptsSynaptic vesicle cycleVesicle cyclePresynaptic autophagyAutophagosome biogenesisATG-9Only transmembrane proteinTrans-Golgi networkCellular degradation pathwayPresynaptic sitesActivity-dependent mannerTransmembrane proteinSynaptojanin 1Synaptic fociBiogenesisAutophagyNeuronal healthDegradation pathwayTraffickingPathwayParkinson's diseaseSynaptic activityNeuronal activityElegansSitesEndocytosis
2020
Absence of Sac2/INPP5F enhances the phenotype of a Parkinson’s disease mutation of synaptojanin 1
Cao M, Park D, Wu Y, De Camilli P. Absence of Sac2/INPP5F enhances the phenotype of a Parkinson’s disease mutation of synaptojanin 1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 12428-12434. PMID: 32424101, PMCID: PMC7275725, DOI: 10.1073/pnas.2004335117.Peer-Reviewed Original ResearchConceptsSynaptojanin 1Sac domain-containing proteinsDisease mutationsDomain-containing proteinsGenome-wide association studiesPD risk lociSynaptic vesicle recyclingEndocytic factorsPD risk genesPhosphatase domainPhosphoinositide phosphataseParkinson's diseaseNumerous genesParkinson’s disease mutationsVesicle recyclingRisk lociAssociation studiesRisk genesInactivating mutationStriatal dopaminergic nerve terminalsGenesOccasional survivorsMutationsDopaminergic nerve terminalsSJ1
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 ResearchConceptsDopaminergic axonsEarly-onset parkinsonism patientsEndocytic dysfunctionNeurological manifestationsParkinsonism patientsDystrophic changesParkinson's diseaseDorsal striatumHuman patientsClathrin-coated intermediatesParkin levelsHomozygous mutationMutant brainsSynaptojanin 1Domain mutationsTerminal changesPatientsStriking accumulationAxonsDiseaseMiceSynapsesSynaptic vesicle endocytosisMutationsDysfunction
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 levelsRegulatorProteinActinEnzymeMembraneDifferential Expression of Endophilin 1 and 2 Dimers at Central Nervous System Synapses*
Ringstad N, Nemoto Y, De Camilli P. Differential Expression of Endophilin 1 and 2 Dimers at Central Nervous System Synapses*. Journal Of Biological Chemistry 2001, 276: 40424-40430. PMID: 11518713, DOI: 10.1074/jbc.m106338200.Peer-Reviewed Original ResearchConceptsEndophilin-1SH3 domain-mediated interactionsDiverse cellular proteinsDomain-mediated interactionsSynaptic vesicle biogenesisNH2-terminal moietyCoiled-coil domainCentral nervous system synapsesGTPase dynaminVesicle biogenesisDifferent cellular targetsEndocytic machineryCellular proteinsSynaptojanin 1Endophilin isoformsRelated proteinsDifferential expressionCellular targetsStable dimerSynaptojaninDynaminSame complexProteinCentral synapsesFamily members
2000
Direct 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
Recruitment 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 Domains
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 evidenceDomain