2022
ER-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
2019
Weak membrane interactions allow Rheb to activate mTORC1 signaling without major lysosome enrichment
Angarola B, Ferguson SM. Weak membrane interactions allow Rheb to activate mTORC1 signaling without major lysosome enrichment. Molecular Biology Of The Cell 2019, 30: 2750-2760. PMID: 31532697, PMCID: PMC6789162, DOI: 10.1091/mbc.e19-03-0146.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAnimalsChlorocebus aethiopsCOS CellsEndoplasmic ReticulumHeLa CellsHumansLysosomesMechanistic Target of Rapamycin Complex 1Monomeric GTP-Binding ProteinsMultiprotein ComplexesNeuropeptidesPrenylationRas Homolog Enriched in Brain ProteinSignal TransductionTOR Serine-Threonine KinasesConceptsMembrane interactionsC-terminal CAAX motifTransient membrane interactionsEndoplasmic reticulum localizationMTOR complex 1CAAX motifRheb GTPaseER membraneMTORC1 activationSubcellular localizationTargeting motifRhebLysosome enrichmentHuman cellsFunctional assaysTargeting mechanismStable interactionStable localizationLysosomesFurther systematic analysisMotifActivation