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 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
Overlapping 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 rolePathology
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