PXD053641-1

PXD053641 is an original dataset announced via ProteomeXchange.

Title	APP and β-amyloid modulate protein aggregation and dissociation from recycling endosomal and exosomal membranes
Description	Secretory proteins frequently aggregate into non-soluble dense-core granules (DCGs) in recycling endosome-like compartments prior to release. By contrast, aberrantly processed Aβ-peptides derived from Amyloid Precursor Protein (APP) form pathological amyloidogenic aggregations in late-stage Alzheimer’s Disease (AD) after secretion. By examining living Drosophila prostate-like secondary cells, we show both APP and Aβ-peptides affect normal DCG biogenesis. These cells generate DCGs and secreted nanovesicles called Rab11-exosomes within enlarged recycling endosomes. The fly APP homologue, APP-like (APPL), associates with these vesicles and the compartmental limiting membrane, from where its extracellular domain controls protein aggregation. Proteolytic release of this domain permits mini-aggregates to coalesce into a large central DCG. Mutant Aβ-peptide expression, like Appl loss-of-function, disrupts this assembly and compartment motility, and increases lysosomal targeting, mirroring pathological events reported in early-stage AD. Our data therefore reveal a physiological role for APP in membrane-dependent protein aggregation, which when disrupted, triggers AD-relevant endolysosomal pathologies.
HostingRepository	PRIDE
AnnounceDate	2025-07-10
AnnouncementXML	Submission_2025-07-10_01:57:47.324.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-04 05:59:19	ID requested
⏵ 1	2025-07-10 01:57:47	announced

10.1038/S44318-025-00497-Y;

submitter keyword: amyloid,Exosomes

Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
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/2025/07/PXD053641

PRIDE project URI

• PRIDE
  1. PXD053641
     1. Label: PRIDE project
     2. Name: APP and β-amyloid modulate protein aggregation and dissociation from recycling endosomal and exosomal membranes