PXD031016-2

PXD031016 is an original dataset announced via ProteomeXchange.

Title	Isoform-dependent lysosomal degradation and internalization of Apolipoprotein E requires autophagy proteins
Description	Alzheimer’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.
HostingRepository	PRIDE
AnnounceDate	2022-01-27
AnnouncementXML	Submission_2022-01-27_07:34:07.005.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joan Steffan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-16 23:13:14	ID requested
1	2022-01-17 16:53:17	announced
⏵ 2	2022-01-27 07:34:07	announced	2022-01-27: Updated project metadata.
3	2023-11-14 08:54:33	announced	2023-11-14: Updated project metadata.

10.1242/JCS.258687;

submitter keyword: Alzheimers APOE APOE4 chaperone-mediated autophagy LC3

Joan Steffan
contact affiliation	Department of Psychiatry and Human Behavior University of California, Irvine
contact email	jssteffa@uci.edu
lab head
Joan Steffan
contact affiliation	Associate Professor, Department of Psychiatry and Human Behavior, University of CA, Irvine,
contact email	jssteffa@uci.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/01/PXD031016

PRIDE project URI

• PRIDE
  1. PXD031016
     1. Label: PRIDE project
     2. Name: Isoform-dependent lysosomal degradation and internalization of Apolipoprotein E requires autophagy proteins