2024
VPS13B is localized at the interface between Golgi cisternae and is a functional partner of FAM177A1
Ugur B, Schueder F, Shin J, Hanna M, Wu Y, Leonzino M, Su M, McAdow A, Wilson C, Postlethwait J, Solnica-Krezel L, Bewersdorf J, De Camilli P. VPS13B is localized at the interface between Golgi cisternae and is a functional partner of FAM177A1. Journal Of Cell Biology 2024, 223: e202311189. PMID: 39331042, PMCID: PMC11451052, DOI: 10.1083/jcb.202311189.Peer-Reviewed Original ResearchConceptsLipid transportGolgi complex proteinGolgi subcompartmentsGolgi membranesGolgi cisternaeProtein familyFunctional partnersGolgi complexKO cellsComplex proteinsFAM177A1GolgiVPS13BAdjacent membranesMutationsProteinCohen syndromeLipidOrthologsInteractorsBrefeldinMembraneOrganellesSubcompartmentsDevelopmental disordersPhosphoglycerate kinase is a central leverage point in Parkinson’s disease–driven neuronal metabolic deficits
Kokotos A, Antoniazzi A, Unda S, Ko M, Park D, Eliezer D, Kaplitt M, De Camilli P, Ryan T. Phosphoglycerate kinase is a central leverage point in Parkinson’s disease–driven neuronal metabolic deficits. Science Advances 2024, 10: eadn6016. PMID: 39167658, PMCID: PMC11338267, DOI: 10.1126/sciadv.adn6016.Peer-Reviewed Original ResearchConceptsPhosphoglycerate kinase 1Metabolic deficitsExpressions of Phosphoglycerate Kinase 1Dopamine axonsParkinson's diseasePD-associated pathologyViral expressionLoss of functionNeuronal glycolysisSusceptibility lociIn vivoFamilial Parkinson's diseasePD therapeuticsMetabolic lesionsProduction kineticsKinase 1Mitochondrial integrityPhosphoglycerate kinaseBioenergetic deficitsSynaptic dysfunctionGenetic originDeficitsPARK7/DJ-1PhosphoglycerateA complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell–cell contacts
Johnson B, Iuliano M, Lam T, Biederer T, De Camilli P. A complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell–cell contacts. Journal Of Cell Biology 2024, 223: e202311137. PMID: 39158698, PMCID: PMC11334333, DOI: 10.1083/jcb.202311137.Peer-Reviewed Original ResearchConceptsPlasma membraneNon-vesicular lipid transferSites of cell contactC-terminus motifsCell contact-dependent signalsContact-dependent signalingCell-cell contactER/PM junctionsTMEM24ER proteinsPM proteinsSynCAM 1Cell adhesion moleculesCellular functionsLipid transferC2CD2Phospholipid transportLipid transportCell contactProteinAdhesion moleculesCalcium homeostasisCellsFamily membersParalogsOverlapping 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 sizeFamilyMiceSynapsinCoexpressionAbundanceSynaptoporinMembersLoss of function of FAM177A1, a Golgi complex localized protein, causes a novel neurodevelopmental disorder
Kohler J, Legro N, Baldridge D, Shin J, Bowman A, Ugur B, Jackstadt M, Shriver L, Patti G, Zhang B, Feng W, McAdow A, Goddard P, Ungar R, Jensen T, Smith K, Fresard L, Alvarez R, Bonner D, Reuter C, McCormack C, Kravets E, Marwaha S, Holt J, Network U, Acosta M, Adam M, Adams D, Alvarez R, Alvey J, Amendola L, Andrews A, Ashley E, Bacino C, Bademci G, Balasubramanyam A, Baldridge D, Bale J, Bamshad M, Barbouth D, Bayrak-Toydemir P, Beck A, Beggs A, Behrens E, Bejerano G, Bellen H, Bennett J, Berg-Rood B, Bernstein J, Berry G, Bican A, Bivona S, Blue E, Bohnsack J, Bonner D, Botto L, Boyd B, Briere L, Burke E, Burrage L, Butte M, Byers P, Byrd W, Carey J, Carrasquillo O, Cassini T, Chang T, Chanprasert S, Chao H, Chinn I, Clark G, Coakley T, Cobban L, Cogan J, Coggins M, Cole F, Colley H, Cope H, Corner B, Corona R, Craigen W, Crouse A, Cunningham M, D’Souza P, Dai H, Dasari S, Davis J, Dayal J, Dell’Angelica E, Dickson P, Dipple K, Doherty D, Dorrani N, Doss A, Douine E, Earl D, Eckstein D, Emrick L, Eng C, Ezell K, Falk M, Fieg E, Fisher P, Fogel B, Forghani I, Gahl W, Glass I, Gochuico B, Goddard P, Godfrey R, Golden-Grant K, Grajewski A, Hadley D, Hahn S, Halley M, Hamid R, Hassey K, Hayes N, High F, Hing A, Hisama F, Holm I, Hom J, Horike-Pyne M, Huang A, Hutchison S, Introne W, Isasi R, Izumi K, Jamal F, Jarvik G, Jarvik J, Jayadev S, Jean-Marie O, Jobanputra V, Karaviti L, Ketkar S, Kiley D, Kilich G, Kobren S, Kohane I, Kohler J, Korrick S, Kozuira M, Krakow D, Krasnewich D, Kravets E, Lalani S, Lam B, Lam C, Lanpher B, Lanza I, LeBlanc K, Lee B, Levitt R, Lewis R, Liu P, Liu X, Longo N, Loo S, Loscalzo J, Maas R, Macnamara E, MacRae C, Maduro V, Maghiro A, Mahoney R, Malicdan M, Mamounas L, Manolio T, Mao R, Maravilla K, Marom R, Marth G, Martin B, Martin M, Martínez-Agosto J, Marwaha S, McCauley J, McConkie-Rosell A, McCray A, McGee E, Mefford H, Merritt J, Might M, Mirzaa G, Morava E, Moretti P, Mulvihill J, Nakano-Okuno M, Nelson S, Neumann S, Newman J, Nicholas S, Nickerson D, Nieves-Rodriguez S, Novacic D, Oglesbee D, Orengo J, Pace L, Pak S, Pallais J, Palmer C, Papp J, Parker N, Phillips J, Posey J, Potocki L, Swerdzewski B, Quinlan A, Rao D, Raper A, Raskind W, Renteria G, Reuter C, Rives L, Robertson A, Rodan L, Rosenfeld J, Rosenwasser N, Rossignol F, Ruzhnikov M, Sacco R, Sampson J, Saporta M, Schaechter J, Schedl T, Schoch K, Scott D, Scott C, Seto E, Shashi V, Shin J, Silverman E, Sinsheimer J, Sisco K, Smith E, Smith K, Solnica-Krezel L, Solomon B, Spillmann R, Stoler J, Sullivan K, Sullivan J, Sun A, Sutton S, Sweetser D, Sybert V, Tabor H, Tan Q, Tan A, Tarakad A, Tekin M, Telischi F, Thorson W, Tifft C, Toro C, Tran A, Ungar R, Urv T, Vanderver A, Velinder M, Viskochil D, Vogel T, Wahl C, Walker M, Wallace S, Walley N, Wambach J, Wan J, Wangler M, Ward P, Wegner D, Hubshman M, Wener M, Wenger T, Westerfield M, Wheeler M, Whitlock J, Wolfe L, Worley K, Xiao C, Yamamoto S, Yang J, Zhang Z, Zuchner S, Worthey E, Ashley E, Montgomery S, Fisher P, Postlethwait J, De Camilli P, Solnica-Krezel L, Bernstein J, Wheeler M. Loss of function of FAM177A1, a Golgi complex localized protein, causes a novel neurodevelopmental disorder. Genetics In Medicine 2024, 26: 101166. PMID: 38767059, PMCID: PMC11451386, DOI: 10.1016/j.gim.2024.101166.Peer-Reviewed Original ResearchNegative regulation of cell proliferationLoss-of-function variantsPathways associated with apoptosisRegulation of cell proliferationRelationship to human diseaseHuman cell linesNeurodevelopmental disordersRNA-seqLocalized proteinsImmune-associated genesZebrafish cellsGolgi complexModel organismsGlobal developmental delayBiallelic variantsFAM177A1Negative regulatorHuman diseasesZebrafish model organismPhysiological functionsCell linesGolgiHuman fibroblastsZebrafishCell proliferationParkinsonism 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(4UbiquitinEndocytosisA serendipitous discovery of a family of membrane remodelling proteins
De Camilli P. A serendipitous discovery of a family of membrane remodelling proteins. Nature Cell Biology 2024, 26: 173-173. PMID: 38307996, DOI: 10.1038/s41556-023-01307-5.Peer-Reviewed Original Research
2023
Membrane remodeling properties of the Parkinson’s disease protein LRRK2
Wang X, Espadas J, Wu Y, Cai S, Ge J, Shao L, Roux A, De Camilli P. Membrane remodeling properties of the Parkinson’s disease protein LRRK2. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2309698120. PMID: 37844218, PMCID: PMC10614619, DOI: 10.1073/pnas.2309698120.Peer-Reviewed Original ResearchEnd-binding protein 1 promotes specific motor-cargo association in the cell body prior to axonal delivery of dense core vesicles
Park J, Xie Y, Miller K, De Camilli P, Yogev S. End-binding protein 1 promotes specific motor-cargo association in the cell body prior to axonal delivery of dense core vesicles. Current Biology 2023, 33: 3851-3864.e7. PMID: 37586371, PMCID: PMC10529979, DOI: 10.1016/j.cub.2023.07.052.Peer-Reviewed Original ResearchConceptsKIF1A/UNCTrans-GolgiDense-core vesiclesEnd-binding protein 1Microtubule growthEnd-binding protein EB1Calponin homology domainMicrotubule-associated proteinsDCV biogenesisCore vesiclesSorting machineryHomology domainAxonal deliveryProtein EB1DCV cargosEndogenous cargoUnrelated proteinsUnexpected roleFunction experimentsGolgiEarly stepsProtein 1UNCNeuronal functionProteinRBG Motif Bridge-Like Lipid Transport Proteins: Structure, Functions, and Open Questions
Hanna M, Guillén-Samander A, De Camilli P. RBG Motif Bridge-Like Lipid Transport Proteins: Structure, Functions, and Open Questions. Annual Review Of Cell And Developmental Biology 2023, 39: 409-434. PMID: 37406299, DOI: 10.1146/annurev-cellbio-120420-014634.Peer-Reviewed Original ResearchLipid transfer proteinMembrane contact sitesVesicle-mediated trafficTransport of lipidsPutative physiological roleEukaryotic cellsEndocytic pathwayContact sitesLipid transportPhysiological roleTransfer proteinProteinHydrophobic channelRod-like structureLipidsEntire lengthDevelopmental disordersCytosolMutationsNew familyTransportPathwayMechanismMembraneCellsATG9 vesicles comprise the seed membrane of mammalian autophagosomes
Olivas T, Wu Y, Yu S, Luan L, Choi P, Guinn E, Nag S, De Camilli P, Gupta K, Melia T. ATG9 vesicles comprise the seed membrane of mammalian autophagosomes. Journal Of Cell Biology 2023, 222: e202208088. PMID: 37115958, PMCID: PMC10148236, DOI: 10.1083/jcb.202208088.Peer-Reviewed Original ResearchConceptsAtg9 vesiclesMammalian autophagosomesStyrene maleic acid lipid particlesLipid scramblase activityLC3-IIAutophagosomes formAutophagosome membraneMature autophagosomesScramblase activityAutophagosome formationAtg9Lipid transportMembrane growthAutophagosomesNanoscale organizationProtein-mediated transferProteinMembrane surface areaOrganellesVesiclesSeed membraneMembraneLipid particlesLipidsDifferent stagesMutations 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 changesDiseaseSynaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates
Park D, Wu Y, Wang X, Gowrishankar S, Baublis A, De Camilli P. Synaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates. Nature Communications 2023, 14: 455. PMID: 36709207, PMCID: PMC9884207, DOI: 10.1038/s41467-023-36081-3.Peer-Reviewed Original ResearchConceptsMembrane proteinsSV membrane proteinsVesicle membrane proteinEctopic expression systemSynaptic vesicle proteinsSynaptic vesicle clustersSV proteinsVesicle proteinsEctopic expressionExpression systemVesicle clustersSynapsinProteinLiquid-like propertiesVesiclesDistinct classesDual roleSynapsin 1FibroblastsATG9ASynapsesExpressionDistinct phasesNerve terminalsClustersErythroid Differentiation Dependent Interaction of VPS13A with XK at the Plasma Membrane of K562 Cells
Amos C, Xu P, De Camilli P. Erythroid Differentiation Dependent Interaction of VPS13A with XK at the Plasma Membrane of K562 Cells. Contact 2023, 6: 25152564231215133. PMID: 38144430, PMCID: PMC10748539, DOI: 10.1177/25152564231215133.Peer-Reviewed Original Research
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 partnershipEndoplasmic Reticulum Membrane Contact Sites, Lipid Transport, and Neurodegeneration.
Guillén-Samander A, De Camilli P. Endoplasmic Reticulum Membrane Contact Sites, Lipid Transport, and Neurodegeneration. Cold Spring Harbor Perspectives In Biology 2022, 15: a041257. PMID: 36123033, PMCID: PMC10071438, DOI: 10.1101/cshperspect.a041257.Peer-Reviewed Original ResearchConceptsMembrane contact sitesEndoplasmic reticulumEndoplasmic reticulum membrane contact sitesContact sitesLipid transportER membrane contact sitesCross talkLipid transfer proteinMutations of genesFamilial neurodegenerative diseasesIntracellular membranous organellesEndomembrane systemLipid trafficVesicular transportCell physiologyPlasma membraneMembranous organellesMembrane lipidsLipid exchangeTransfer proteinCell compartmentProteinNeurodegenerative diseasesMultiplicity of rolesDendritic tipsA 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 transferERSyndromeDiseaseIn situ architecture of the lipid transport protein VPS13C at ER–lysosome membrane contacts
Cai S, Wu Y, Guillén-Samander A, Hancock-Cerutti W, Liu J, De Camilli P. In situ architecture of the lipid transport protein VPS13C at ER–lysosome membrane contacts. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2203769119. PMID: 35858323, PMCID: PMC9303930, DOI: 10.1073/pnas.2203769119.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumCryo-focused ion beam millingMembrane contact sitesCryo-electron tomographyFull-length structureLipid transport proteinsRod-like densitiesLysosome contactBinding partnerGenetic approachesHydrophobic grooveTransport proteinsContact sitesVps13Lipid transportAlphaFold predictionsFull-length modelHeLa cellsMembrane contactSitu architectureAdjacent membranesVPS13CProteinStructural informationEndo/lysosomesER-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 proteinActivationCellsPathwayNovel pathways of intracellular membrane lipid transport and neurodegenerative diseases
De Camilli P. Novel pathways of intracellular membrane lipid transport and neurodegenerative diseases. The FASEB Journal 2022, 36 DOI: 10.1096/fasebj.2022.36.s1.0i152.ChaptersFamily proteinsLipid transportMembrane lipid transportMembrane contact sitesLipid binding modulesLipid transport proteinsLipid trafficRod-like proteinsBinding modulesHydrophobic grooveTransport proteinsContact sitesMembrane lipidsFunction mutationsLipid transferNovel pathwayNeurodevelopmental diseasesProteinVesicular carriersFamily resultsNeurodegenerative diseasesChorea-AcanthocytosisPotential roleNew mechanismMembrane