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 disorders
2022
In 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 proteinActivationCellsPathway
2021
VPS13D 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 domainEukaryotesGem1MetazoansER
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 confinementCellsNeurosporaOrganellesHeterodimersVIVIDProtein
2018
VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites
Kumar N, Leonzino M, Hancock-Cerutti W, Horenkamp FA, Li P, Lees JA, Wheeler H, Reinisch KM, De Camilli P. VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites. Journal Of Cell Biology 2018, 217: 3625-3639. PMID: 30093493, PMCID: PMC6168267, DOI: 10.1083/jcb.201807019.Peer-Reviewed Original ResearchConceptsN-terminal portionAutophagy protein ATG2Membrane lipid homeostasisLate endosomes/lysosomesSecondary structure similarityLipid transport proteinsER contact sitesEndosomes/lysosomesHuman VPS13AVPS13 genesVps13Implicating defectsTransport proteinsLipid transportersContact sitesGenetic studiesLipid homeostasisLipid exchangeTransport roleProteinOrganellesVPS13ANeurodegenerative disordersStructure similarityHydrophobic cavity
2017
Lipid transport by TMEM24 at ER–plasma membrane contacts regulates pulsatile insulin secretion
Lees JA, Messa M, Sun EW, Wheeler H, Torta F, Wenk MR, De Camilli P, Reinisch KM. Lipid transport by TMEM24 at ER–plasma membrane contacts regulates pulsatile insulin secretion. Science 2017, 355 PMID: 28209843, PMCID: PMC5414417, DOI: 10.1126/science.aah6171.Peer-Reviewed Original ResearchConceptsER–plasma membrane contactsLipid transportLipid-binding modulesMembrane contactPhosphoinositide signalingMembrane proteinsPrecursor phosphatidylinositolProtein 24Reversible localizationEndoplasmic reticulumTMEM24Β-cellsPhosphatidylinositolInsulin secretionCalcium oscillationsCytosolic calciumDephosphorylationType II diabetesPhosphorylationSignalingProteinReticulumSecretionII diabetesTransport
2016
Endosome-ER Contacts Control Actin Nucleation and Retromer Function through VAP-Dependent Regulation of PI4P
Dong R, Saheki Y, Swarup S, Lucast L, Harper JW, De Camilli P. Endosome-ER Contacts Control Actin Nucleation and Retromer Function through VAP-Dependent Regulation of PI4P. Cell 2016, 166: 408-423. PMID: 27419871, PMCID: PMC4963242, DOI: 10.1016/j.cell.2016.06.037.Peer-Reviewed Original ResearchControl of plasma membrane lipid homeostasis by the extended synaptotagmins
Saheki Y, Bian X, Schauder CM, Sawaki Y, Surma MA, Klose C, Pincet F, Reinisch KM, De Camilli P. Control of plasma membrane lipid homeostasis by the extended synaptotagmins. Nature Cell Biology 2016, 18: 504-515. PMID: 27065097, PMCID: PMC4848133, DOI: 10.1038/ncb3339.Peer-Reviewed Original ResearchConceptsSMP domainE-Syt1ER-PM tethersMembrane lipid homeostasisPlasma membrane lipidsEndoplasmic reticulum proteinAccumulation of diacylglycerolE-SytsExtended synaptotagminsMolecular basisMajor glycerolipidsReticulum proteinsMetabolic recyclingMembrane lipidsLipid homeostasisPLC activationSynaptotagminSustained accumulationHomeostatic responseDiacylglycerolGlycerolipidsMetabolic changesGenomeCa2Accumulation
2015
PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER–plasma membrane contacts
Chung J, Torta F, Masai K, Lucast L, Czapla H, Tanner LB, Narayanaswamy P, Wenk MR, Nakatsu F, De Camilli P. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER–plasma membrane contacts. Science 2015, 349: 428-432. PMID: 26206935, PMCID: PMC4638224, DOI: 10.1126/science.aab1370.Peer-Reviewed Original ResearchConceptsPlasma membraneEndoplasmic reticulumER integral membrane proteinsER–plasma membrane contactsMembrane lipid homeostasisIntegral membrane proteinsPleckstrin homology domainOxysterol-binding proteinPI4P phosphatase Sac1PI4P levelsCell membrane bilayerHomology domainPhosphatase Sac1Membrane proteinsORP8Function experimentsMembrane bilayerLipid homeostasisLipid transferProtein 5Membrane contactORP5PI4PPhosphatidylserineProtein
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