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PXD031016-2

PXD031016 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIsoform-dependent lysosomal degradation and internalization of Apolipoprotein E requires autophagy proteins
DescriptionAlzheimer’s disease (AD), and lysosomal dysfunction has been implicated in AD pathogenesis. We found, by examining cells stably expressing each APOE isoform, that APOE4 increases lysosomal trafficking, accumulates in enlarged lysosomes and late endosomes, alters autophagic flux and the abundance of autophagy proteins and lipid droplets, and alters the proteomic contents of lysosomes following internalization. We investigated APOE-related lysosomal trafficking further in cell culture, and found that APOE from the post-Golgi compartment is degraded through autophagy. We found that this autophagic process requires the lysosomal membrane protein LAMP2 in immortalized neuron-like and hepatic cells, and in mouse brain tissue. Several macroautophagy-associated proteins were also required for autophagic degradation and internalization of APOE in hepatic cells. The dysregulated autophagic flux and lysosomal trafficking of APOE4 that we observed suggest a possible novel mechanism that might contribute to AD pathogenesis.
HostingRepositoryPRIDE
AnnounceDate2022-01-27
AnnouncementXMLSubmission_2022-01-27_07:34:07.005.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJoan Steffan
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-01-16 23:13:14ID requested
12022-01-17 16:53:17announced
22022-01-27 07:34:07announced2022-01-27: Updated project metadata.
Publication List
10.1242/JCS.258687;
Keyword List
submitter keyword: Alzheimers APOE APOE4 chaperone-mediated autophagy LC3
Contact List
Joan Steffan
contact affiliationDepartment of Psychiatry and Human Behavior University of California, Irvine
contact emailjssteffa@uci.edu
lab head
Joan Steffan
contact affiliationAssociate Professor, Department of Psychiatry and Human Behavior, University of CA, Irvine,
contact emailjssteffa@uci.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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