2024
A 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 ResearchMeSH KeywordsAnimalsBiological TransportCalciumCell CommunicationCell MembraneEndoplasmic ReticulumHEK293 CellsHumansLipid MetabolismMembrane ProteinsMiceProtein BindingConceptsPlasma 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 membersParalogs
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 ResearchMeSH KeywordsCarrier ProteinsCell MembraneEndoplasmic ReticulumHumansLipidsNeuroacanthocytosisVesicular Transport ProteinsConceptsCaudate 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 proteinActivationCellsPathway
2021
Stepwise membrane binding of extended synaptotagmins revealed by optical tweezers
Ge J, Bian X, Ma L, Cai Y, Li Y, Yang J, Karatekin E, De Camilli P, Zhang Y. Stepwise membrane binding of extended synaptotagmins revealed by optical tweezers. Nature Chemical Biology 2021, 18: 313-320. PMID: 34916620, PMCID: PMC8891060, DOI: 10.1038/s41589-021-00914-3.Peer-Reviewed Original ResearchVPS13D 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
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 bilayersReticulum
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
Contacts between the endoplasmic reticulum and other membranes in neurons
Wu Y, Whiteus C, Xu CS, Hayworth KJ, Weinberg RJ, Hess HF, De Camilli P. Contacts between the endoplasmic reticulum and other membranes in neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e4859-e4867. PMID: 28559323, PMCID: PMC5474793, DOI: 10.1073/pnas.1701078114.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumER–plasma membrane contactsER-PM contactsMembrane contactSmaller focal contactsRegulation of CaInterorganelle communicationOrganelle biogenesisDifferent neuronal compartmentsCell physiologyIntracellular membranesFocal contactsMultivesicular bodiesER contactsIntracellular organellesER cisternaeLipid homeostasisBiochemical studiesTubulovesicular structuresMembrane appositionNeuronal compartmentsImportant functionsMitochondriaReticulumMembraneEndoplasmic Reticulum—Plasma Membrane Contact Sites
Saheki Y, De Camilli P. Endoplasmic Reticulum—Plasma Membrane Contact Sites. Annual Review Of Biochemistry 2017, 86: 1-26. PMID: 28301744, DOI: 10.1146/annurev-biochem-061516-044932.Peer-Reviewed Original ResearchConceptsPlasma membraneEndoplasmic reticulumProtein tethersEndoplasmic reticulum-plasma membrane contact sitesNonvesicular lipid transportER-PM contactsMembrane contact sitesLipid transfer proteinLipid trafficCell physiologyContact sitesMembranous organellesLipid transportBroad localizationTransfer proteinCross talkIntracellular CaDirect physical contactMultiplicity of rolesFunctional stateLipid 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
SMP-domain proteins at membrane contact sites: Structure and function
Reinisch KM, De Camilli P. SMP-domain proteins at membrane contact sites: Structure and function. Biochimica Et Biophysica Acta 2015, 1861: 924-927. PMID: 26686281, PMCID: PMC4902782, DOI: 10.1016/j.bbalip.2015.12.003.Peer-Reviewed Original ResearchConceptsMembrane contact sitesContact sitesAnant K. MenonCellular lipid landscapeTim P. LevineER-mitochondrial contactsSMP domainLipid landscapeComplex subunitsPlasma membraneMolecular basisLipid transportersEndoplasmic reticulumProteinRecent discoveryMembraneSuch sitesSitesSubunitsReticulumTransportersGlycerolipidsRegulationElucidationSpecial issuePI4P/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
2000
Functional Characterization of a Mammalian Sac1 and Mutants Exhibiting Substrate-specific Defects in Phosphoinositide Phosphatase Activity*
Nemoto Y, Kearns B, Wenk M, Chen H, Mori K, Alb J, De Camilli P, Bankaitis V. Functional Characterization of a Mammalian Sac1 and Mutants Exhibiting Substrate-specific Defects in Phosphoinositide Phosphatase Activity*. Journal Of Biological Chemistry 2000, 275: 34293-34305. PMID: 10887188, DOI: 10.1074/jbc.m003923200.Peer-Reviewed Original ResearchConceptsSubstrate-specific defectsIntegral membrane proteinsPhosphoinositide phosphatase activityPhosphatase activityMembrane proteinsEndoplasmic reticulumGolgi secretory functionIntegral membrane lipidEukaryotic cell physiologyPrimary sequence homologyYeast Sac1pSAC1 geneHeterologous complementationActin functionSac1 domainSac1pBisphosphate substrateMembrane phosphoinositidesPhosphatidylinositol 3Cell physiologyFunctional characterizationGene productsSequence homologyProtein activityGolgi complex
1996
Yeast protein translocation complex: Isolation of two genes SEB1 and SEB2 encoding proteins homologous to the Sec61β subunit
Toikkanen J, Gatti E, Takei K, Saloheimo M, Olkkonen V, Söderlund H, De Camilli P, Keränen S. Yeast protein translocation complex: Isolation of two genes SEB1 and SEB2 encoding proteins homologous to the Sec61β subunit. Yeast 1996, 12: 425-438. PMID: 8740416, DOI: 10.1002/(sici)1097-0061(199604)12:5<425::aid-yea924>3.0.co;2-b.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBiological TransportCell LineChlorocebus aethiopsCloning, MolecularCytoplasmDNA, ComplementaryDogsEndoplasmic ReticulumFungal ProteinsGenes, FungalGenes, SuppressorMembrane ProteinsMembrane Transport ProteinsMicrosomesMolecular Sequence DataMolecular WeightSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSEC Translocation ChannelsSequence Analysis, DNASequence Homology, Amino AcidVesicular Transport ProteinsConceptsBeta subunitN-terminal signal sequencePotential membrane-spanning regionsEndoplasmic reticulumProtein translocation apparatusMembrane-spanning regionNovel genetic toolsTemperature-sensitive phenotypeHydrophilic N-terminusEvolutionary conservationTranslocation apparatusYeast genesHeterologous hybridizationProtein translocationHomologous genesER membraneGenetic toolsSignal sequenceChromosomal disruptionMulticopy plasmidC-terminusDouble disruptionN-terminusFunctional analysisSeb1
1990
lnsP3 receptor turnaround
DE CAMILLI P, TAKEI K, MIGNERY G, SÜDHOF T. lnsP3 receptor turnaround. Nature 1990, 344: 495-495. PMID: 2157163, DOI: 10.1038/344495a0.Peer-Reviewed Original Research