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 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 membersParalogs
2022
Endoplasmic 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/lysosomes
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 Research
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
2017
Endoplasmic 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
Control 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 issueThe leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane
Baskin JM, Wu X, Christiano R, Oh MS, Schauder CM, Gazzerro E, Messa M, Baldassari S, Assereto S, Biancheri R, Zara F, Minetti C, Raimondi A, Simons M, Walther TC, Reinisch KM, De Camilli P. The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane. Nature Cell Biology 2015, 18: 132-138. PMID: 26571211, PMCID: PMC4689616, DOI: 10.1038/ncb3271.Peer-Reviewed Original ResearchPI4P/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
2001
Generation of high curvature membranes mediated by direct endophilin bilayer interactions
Farsad K, Ringstad N, Takei K, Floyd S, Rose K, De Camilli P. Generation of high curvature membranes mediated by direct endophilin bilayer interactions. Journal Of Cell Biology 2001, 155: 193-200. PMID: 11604418, PMCID: PMC2198845, DOI: 10.1083/jcb.200107075.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsBiological TransportCarrier ProteinsCell MembraneCell SizeDynaminsGolgi ApparatusGTP PhosphohydrolasesHumansLipid BilayersMacromolecular SubstancesMolecular Sequence DataNerve Tissue ProteinsPhylogenyProtein Structure, TertiaryRatsSequence Homology, Amino AcidSynaptic VesiclesConceptsEndophilin-1Lipid bilayersMembrane-trafficking eventsAmino acid stretchHigh-curvature membranesNH2-terminal regionCell-free systemEndophilin BEndophilin functionGTPase dynaminDynamin ringsVesicle buddingEndophilinEndocytic vesiclesGolgi complexNarrow tubulesMembrane deformationCorresponding regionProteinTransferase activityAcyl transferase activityBilayer interactionsNew insightsLipid tubulesPotential role
2000
A Functional Link between Dynamin and the Actin Cytoskeleton at Podosomes
Ochoa G, Slepnev V, Neff L, Ringstad N, Takei K, Daniell L, Kim W, Cao H, McNiven M, Baron R, De Camilli P. A Functional Link between Dynamin and the Actin Cytoskeleton at Podosomes. Journal Of Cell Biology 2000, 150: 377-390. PMID: 10908579, PMCID: PMC2180219, DOI: 10.1083/jcb.150.2.377.Peer-Reviewed Original ResearchConceptsDynamin 2Rous sarcoma virus resultsFunctional linkAttachment sitesDynamin familyActin cytoskeletonActin turnoverGFP-actinAdhesion structuresPlasma membranePodosomesAdhesion plaquesDynaminCell transformationNontransformed cellsTubular invaginationsFluorescence recoverySimilar turnoverActinSubstratumVirus resultsCellsTurnoverCytoskeletonDramatic changes
1999
AP-2 Recruitment to Synaptotagmin Stimulated by Tyrosine-Based Endocytic Motifs
Haucke V, De Camilli P. AP-2 Recruitment to Synaptotagmin Stimulated by Tyrosine-Based Endocytic Motifs. Science 1999, 285: 1268-1271. PMID: 10455054, DOI: 10.1126/science.285.5431.1268.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex alpha SubunitsAdaptor Proteins, Vesicular TransportAnimalsBinding SitesCalcium-Binding ProteinsCattleCell MembraneCHO CellsClathrinCoated Pits, Cell-MembraneCricetinaeEndocytosisMembrane GlycoproteinsMembrane ProteinsNerve Tissue ProteinsNeuronsOligopeptidesPhospholipase DProtein BindingRatsRecombinant Fusion ProteinsSynaptic MembranesSynaptotagminsTyrosineConceptsAP-2 recruitmentEndocytic motifAP-2Cargo proteinsPlasma membraneTyrosine-based endocytic motifClathrin adaptor protein AP-2Adaptor protein AP-2Nucleation of clathrinNon-neuronal cellsProtein synaptotagminDocking siteSynaptotagminClathrinMotifProteinRecruitmentMembraneEndocytosisTyrosineBindingCellsPeptides
1998
Perturbation of Dynamin II with an Amphiphysin SH3 Domain Increases GLUT4 Glucose Transporters at the Plasma Membrane in 3T3-L1 Adipocytes DYNAMIN II PARTICIPATES IN GLUT4 ENDOCYTOSIS*
Volchuk A, Narine S, Foster L, Grabs D, De Camilli P, Klip A. Perturbation of Dynamin II with an Amphiphysin SH3 Domain Increases GLUT4 Glucose Transporters at the Plasma Membrane in 3T3-L1 Adipocytes DYNAMIN II PARTICIPATES IN GLUT4 ENDOCYTOSIS*. Journal Of Biological Chemistry 1998, 273: 8169-8176. PMID: 9525921, DOI: 10.1074/jbc.273.14.8169.Peer-Reviewed Original ResearchConceptsGLUT4 endocytosisDynamin IIGLUT4 glucose transportersPlasma membraneCell surfaceSH3 domainClathrin-coated vesicle formationFusion proteinGlucose transporterLevels of GLUT4Amphiphysin SH3 domainLow-density microsomal fractionIsolated plasma membranesTransferrin endocytosisEndocytic systemGLUT4 internalizationProtein dynaminGlutathione S-transferaseEndosomal compartmentsGLUT4 distributionVesicle formationDynamin peptideEndocytosisGLUT4S-transferase
1997
Synaptic Vesicle Endocytosis Impaired by Disruption of Dynamin-SH3 Domain Interactions
Shupliakov O, Löw P, Grabs D, Gad H, Chen H, David C, Takei K, De Camilli P, Brodin L. Synaptic Vesicle Endocytosis Impaired by Disruption of Dynamin-SH3 Domain Interactions. Science 1997, 276: 259-263. PMID: 9092476, DOI: 10.1126/science.276.5310.259.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesCell MembraneCoated Pits, Cell-MembraneDynaminsEndocytosisGTP PhosphohydrolasesHumansLampreysMicroscopy, ElectronMolecular Sequence DataNerve Tissue ProteinsProlineRecombinant Fusion ProteinsSrc Homology DomainsSynapsesSynaptic TransmissionSynaptic VesiclesConceptsSynaptic vesicle endocytosisSH3 domainVesicle endocytosisSrc homology 3 (SH3) domain-containing proteinsDomain-containing proteinsClathrin-coated pitsClathrin-mediated endocytosisSH3 binding siteAmphiphysin SH3 domainSynaptic vesicle recyclingCOOH-terminal regionDynamin bindsDynamin functionBinding partnerVesicle recyclingDomain interactionsDynamin peptidePhysiological roleEndocytosisEssential roleBinding sitesSynaptic architectureSH3DomainAmphiphysinRecycling of Synaptic Vesicles
Bauerfeind R, David C, Grabs D, McPherson P, Nemoto Y, Slepnev V, Takei K, De Camilli P. Recycling of Synaptic Vesicles. Advances In Pharmacology 1997, 42: 253-257. PMID: 9327892, DOI: 10.1016/s1054-3589(08)60741-3.Peer-Reviewed Original ResearchConceptsSynaptic vesicle endocytosisSynaptic vesicle recyclingVesicle endocytosisVesicle recyclingSynaptic vesiclesPlasma membraneClathrin adaptor complex AP2Vesicular transport stepsClathrin-coated vesiclesClathrin-coated pitsMicrotubule-binding proteinSynaptic vesicle cycleRole of proteinsCell surface receptorsRole of lipidsClathrin coatRestrictive temperatureEarly endosomesGuanosine triphosphataseRecycling pathwayVesicle cycleDynaminTransport stepsEndocytosisSurface receptors
1996
Phosphoinositides as Regulators in Membrane Traffic
De Camilli P, Emr S, McPherson P, Novick P. Phosphoinositides as Regulators in Membrane Traffic. Science 1996, 271: 1533-1539. PMID: 8599109, DOI: 10.1126/science.271.5255.1533.Peer-Reviewed Original ResearchConceptsMembrane trafficActivation of proteinsGuanosine triphosphatasesSignal transductionVesicular transportRegulatory mechanismsPhosphatidylinositol metabolitesSecond messengerLocation signalPhosphorylated productsCell surfaceClassical rolePhosphoinositideCritical rolePhosphatidylinositolTransductionTriphosphatasesRegulatorProteinMessengerRegulationPolar headRoleRecruitmentActivation