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
Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines
Falahati H, Wu Y, Feuerer V, Simon HG, De Camilli P. Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2203750119. PMID: 36215465, PMCID: PMC9586327, DOI: 10.1073/pnas.2203750119.Peer-Reviewed Original ResearchConceptsSpine apparatusDendritic spinesSubset of neuronsAxon initial segmentDendritic shaftsER cisternsNonneuronal cellsSynaptopodinSpineSmooth endoplasmic reticulumEndoplasmic reticulumCisternal organelleInitial segmentSpecific localizationCisternsBinding proteinPDLIM7Expression patternsSubsetProteinSmall subsetDiseaseNeuronsBrainFunctional partnershipA partnership between the lipid scramblase XK and the lipid transfer protein VPS13A at the plasma membrane
Guillén-Samander A, Wu Y, Pineda SS, García FJ, Eisen JN, Leonzino M, Ugur B, Kellis M, Heiman M, De Camilli P. A partnership between the lipid scramblase XK and the lipid transfer protein VPS13A at the plasma membrane. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2205425119. PMID: 35994651, PMCID: PMC9436381, DOI: 10.1073/pnas.2205425119.Peer-Reviewed Original ResearchConceptsCaudate neuronsClinical manifestationsExposure of PtdSerPH domainMcLeod syndromeCell surface exposureER-PM contactsLipid dropletsTransport of lipidsPutative roleUnknown mechanismNeuronsLipid transfer proteinVPS13ALipid scramblasesTransfer proteinCytosolic loopExposurePlasma membraneCell surfaceEndoplasmic reticulumLipid transferERSyndromeDiseaseER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling
Hancock-Cerutti W, Wu Z, Xu P, Yadavalli N, Leonzino M, Tharkeshwar AK, Ferguson SM, Shadel GS, De Camilli P. ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling. Journal Of Cell Biology 2022, 221: e202106046. PMID: 35657605, PMCID: PMC9170524, DOI: 10.1083/jcb.202106046.Peer-Reviewed Original ResearchConceptsParkinson's diseasePD pathogenesisLeucine-rich repeat kinase 2 (LRRK2) G2019S mutationCGAS-STING pathwayAccumulation of lysosomesDNA-sensing cGAS-STING pathwayImmune activationLipid profileSTING signalingG2019S mutationAutosomal recessive Parkinson's diseaseRecessive Parkinson's diseaseModel human cell linesHuman cell linesCell linesPathogenesisLate endosomes/lysosomesDiseaseVPS13CEndosomes/lysosomesCurrent studyTransfer proteinActivationCellsPathway
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