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 membersParalogsParkinsonism 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
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 Research
2022
A 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 proteinActivationCellsPathwayJIP3 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 Research
2021
How a first research experience had an impact on my scientific journey
De Camilli P. How a first research experience had an impact on my scientific journey. Molecular Biology Of The Cell 2021, 32: ae1. PMID: 34735266, PMCID: PMC8694089, DOI: 10.1091/mbc.e21-08-0397.Peer-Reviewed Original ResearchBiallelic PI4KA variants cause neurological, intestinal and immunological disease
Salter CG, Cai Y, Lo B, Helman G, Taylor H, McCartney A, Leslie JS, Accogli A, Zara F, Traverso M, Fasham J, Lees JA, Ferla M, Chioza BA, Wenger O, Scott E, Cross HE, Crawford J, Warshawsky I, Keisling M, Agamanolis D, Melver C, Cox H, Elawad M, Marton T, Wakeling M, Holzinger D, Tippelt S, Munteanu M, Valcheva D, Deal C, Van Meerbeke S, Vockley C, Butte MJ, Acar U, van der Knaap MS, Korenke GC, Kotzaeridou U, Balla T, Simons C, Uhlig HH, Crosby AH, De Camilli P, Wolf NI, Baple EL. Biallelic PI4KA variants cause neurological, intestinal and immunological disease. Brain 2021, 144: 3597-3610. PMID: 34415310, PMCID: PMC8719846, DOI: 10.1093/brain/awab313.Peer-Reviewed Original ResearchConceptsOrgan-specific functionsSequence alterationsStructural modelling studyMultiple cell typesCombinatorial biologyHeterotetrameric complexLipid kinasesMolecular partnersFundamental new insightsPhenotypical outcomesFunctional interactionCell typesMembrane phospholipidsTTC7PhosphatidylinositolCritical roleGene alterationsNew insightsHypomyelinating leukodystrophyEfr3Molecular complexesIIIαPI4KAKinaseComplexesInsights into VPS13 properties and function reveal a new mechanism of eukaryotic lipid transport
Leonzino M, Reinisch KM, De Camilli P. Insights into VPS13 properties and function reveal a new mechanism of eukaryotic lipid transport. Biochimica Et Biophysica Acta (BBA) - Molecular And Cell Biology Of Lipids 2021, 1866: 159003. PMID: 34216812, PMCID: PMC8325632, DOI: 10.1016/j.bbalip.2021.159003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagosomesAutophagy-Related ProteinsCryoelectron MicroscopyDisease Models, AnimalEukaryotic CellsHeredodegenerative Disorders, Nervous SystemHumansHydrophobic and Hydrophilic InteractionsLipid BilayersLipid MetabolismMitochondrial MembranesMutationProtein DomainsStructure-Activity RelationshipVesicular Transport ProteinsYeastsConceptsLipid transportMembrane contact sitesDomain protein familyOccurrence of proteinsVPS13 proteinsEukaryotic cellsNumerous proteinsProtein familyIntracellular membranesProtein bridgeHydrophobic grooveContact sitesMembrane growthLipid transferBilayer lipidsNovel mechanismVps13New mechanismProteinLipidsAtg2OrganellesAdjacent bilayersDiscoveryMechanismVPS13D bridges the ER to mitochondria and peroxisomes via Miro
Guillén-Samander A, Leonzino M, Hanna MG, Tang N, Shen H, De Camilli P. VPS13D bridges the ER to mitochondria and peroxisomes via Miro. Journal Of Cell Biology 2021, 220: e202010004. PMID: 33891013, PMCID: PMC8077184, DOI: 10.1083/jcb.202010004.Peer-Reviewed Original ResearchConceptsLipid transport proteinsHigher eukaryotesER-mitochondriaSecretory pathwayAccessory factorsMitochondrial dynamicsDisease pathogenesisTransport proteinsParkin substratesLipid transferSplice variantsParkinson's disease pathogenesisVps13Lipid supplyMitochondriaMiroVPS13DERMESYeastMost lipidsTransport domainEukaryotesGem1MetazoansEROverlapping 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 rolePathologyCooperative function of synaptophysin and synapsin in the generation of synaptic vesicle-like clusters in non-neuronal cells
Park D, Wu Y, Lee SE, Kim G, Jeong S, Milovanovic D, De Camilli P, Chang S. Cooperative function of synaptophysin and synapsin in the generation of synaptic vesicle-like clusters in non-neuronal cells. Nature Communications 2021, 12: 263. PMID: 33431828, PMCID: PMC7801664, DOI: 10.1038/s41467-020-20462-z.Peer-Reviewed Original ResearchConceptsNon-neuronal cellsSV clustersSynaptic vesiclesSmall synaptic-like microvesiclesSV membrane proteinsSynaptic-like microvesiclesSV proteinsDiffuse cytosolic distributionMembrane proteinsReconstitution systemCytosolic distributionCooperative functionSuch vesiclesMechanistic insightsLiquid-like propertiesPowerful modelPhysiological formationProteinSynapsinVesiclesCellsSynaptic transmissionAssembly of structuresDefining featureLiquid condensate
2020
Optimized Vivid-derived Magnets photodimerizers for subcellular optogenetics in mammalian cells
Benedetti L, Marvin JS, Falahati H, Guillén-Samander A, Looger LL, De Camilli P. Optimized Vivid-derived Magnets photodimerizers for subcellular optogenetics in mammalian cells. ELife 2020, 9: e63230. PMID: 33174843, PMCID: PMC7735757, DOI: 10.7554/elife.63230.Peer-Reviewed Original ResearchConceptsProtein fusion partnersSmall subcellular volumesSubcellular optogeneticsOrganelle contactsHomodimerization interfaceProtein modulesMammalian cellsBiological processesPhysiological processesSubcellular organellesLow temperature preincubationSimultaneous photoactivationFusion partnerCell preincubationWhole cellsSubcellular volumesConcatemerizationSpatial controlSpatiotemporal confinementCellsNeurosporaOrganellesHeterodimersVIVIDProteinRole of VPS13, a protein with similarity to ATG2, in physiology and disease
Ugur B, Hancock-Cerutti W, Leonzino M, De Camilli P. Role of VPS13, a protein with similarity to ATG2, in physiology and disease. Current Opinion In Genetics & Development 2020, 65: 61-68. PMID: 32563856, PMCID: PMC7746581, DOI: 10.1016/j.gde.2020.05.027.Peer-Reviewed Original ResearchConceptsAutophagy protein ATG2N-terminal halfVPS13 proteinsMolecular functionsCellular processesFamily proteinsVps13Contact sitesAtg2Intracellular organellesFunctional studiesNovel mechanismProteinSimilar roleHydrophobic channelStructural studiesNeurodegenerative disordersPhysiologyDirect transferOrganellesSimilarityMutationsRoleLipidsBilayersAbsence 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
2019
PDZD8 mediates a Rab7-dependent interaction of the ER with late endosomes and lysosomes
Guillén-Samander A, Bian X, De Camilli P. PDZD8 mediates a Rab7-dependent interaction of the ER with late endosomes and lysosomes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22619-22623. PMID: 31636202, PMCID: PMC6842579, DOI: 10.1073/pnas.1913509116.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumLipid transportLate endosomes/lysosomesIntrinsic membrane proteinsLipid transport proteinsEndosomes/lysosomesEndocytic membranesDomain familyMembrane proteinsLate endosomesEndocytic flowMolecular inventoryTransport proteinsPDZD8ProteinLysosomesMembraneEndosomesAdjacent bilayersReticulumSynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse
Koopmans F, van Nierop P, Andres-Alonso M, Byrnes A, Cijsouw T, Coba M, Cornelisse L, Farrell R, Goldschmidt H, Howrigan D, Hussain N, Imig C, de Jong A, Jung H, Kohansalnodehi M, Kramarz B, Lipstein N, Lovering R, MacGillavry H, Mariano V, Mi H, Ninov M, Osumi-Sutherland D, Pielot R, Smalla K, Tang H, Tashman K, Toonen R, Verpelli C, Reig-Viader R, Watanabe K, van Weering J, Achsel T, Ashrafi G, Asi N, Brown T, De Camilli P, Feuermann M, Foulger R, Gaudet P, Joglekar A, Kanellopoulos A, Malenka R, Nicoll R, Pulido C, de Juan-Sanz J, Sheng M, Südhof T, Tilgner H, Bagni C, Bayés À, Biederer T, Brose N, Chua J, Dieterich D, Gundelfinger E, Hoogenraad C, Huganir R, Jahn R, Kaeser P, Kim E, Kreutz M, McPherson P, Neale B, O'Connor V, Posthuma D, Ryan T, Sala C, Feng G, Hyman S, Thomas P, Smit A, Verhage M. SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse. Neuron 2019, 103: 217-234.e4. PMID: 31171447, PMCID: PMC6764089, DOI: 10.1016/j.neuron.2019.05.002.Peer-Reviewed Original Research