PXD040361-1

PXD040361 is an original dataset announced via ProteomeXchange.

Title	Accessory ESCRT-III proteins are conserved and selective regulators of Rab11a-exosome formation
Description	Exosomes are secreted nanovesicles with potent signalling activity that are initially formed as intraluminal vesicles (ILVs) in late Rab7-positive multivesicular endosomes, and also in recycling Rab11a-positive endosomes, particularly under some forms of nutrient stress. The core proteins of the Endosomal Sorting Complex Required for Transport (ESCRT) participate in exosome biogenesis and ILV-mediated destruction of ubiquitinylated cargos. Accessory ESCRT-III components have reported roles in ESCRT-III-mediated vesicle scission, but their precise functions are poorly defined. They frequently only appear essential under stress. Comparative proteomics analysis of human small extracellular vesicles revealed that accessory ESCRT-III proteins, CHMP1A, CHMP1B, CHMP5 and IST1, are increased in Rab11a-enriched exosome preparations. We show that these proteins are required to form ILVs in Drosophila secondary cell recycling endosomes, but unlike core ESCRTs, they are not involved in degradation of ubiquitinylated proteins in late endosomes. Furthermore, CHMP5 knockdown in human HCT116 colorectal cancer cells selectively inhibits Rab11a-exosome production. Accessory ESCRT-III knockdown suppresses seminal fluid-mediated reproductive signalling by secondary cells and the growth-promoting activity of Rab11a-exosome-containing EVs from HCT116 cells. We conclude that accessory ESCRT-III components have a specific, ubiquitin-independent role in Rab11a-exosome generation, a mechanism that might be targeted to selectively block pro-tumorigenic activities of these vesicles in cancer.
HostingRepository	PRIDE
AnnounceDate	2024-08-02
AnnouncementXML	Submission_2024-08-02_03:50:10.680.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	2023-02-23 03:58:35	ID requested
⏵ 1	2024-08-02 03:50:11	announced
2	2024-10-22 06:52:10	announced	2024-10-22: Updated project metadata.

Marie PP, Fan SJ, Mason J, Wells A, Mendes CC, Wainwright SM, Scott S, Fischer R, Harris AL, Wilson C, Goberdhan DCI, Accessory ESCRT-III proteins are conserved and selective regulators of Rab11a-exosome formation. J Extracell Vesicles, 12(3):e12311(2023) [pubmed]

10.1002/jev2.12311;

submitter keyword: ESCRT/ CHMP5/ extracellular vesicle/ Rab11a-exosome/ recycling endosome

Roman Fischer
contact affiliation	Discovery Proteomics University of Oxford Target Discovery Institute
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/2024/08/PXD040361

PRIDE project URI

• PRIDE
  1. PXD040361
     1. Label: PRIDE project
     2. Name: Accessory ESCRT-III proteins are conserved and selective regulators of Rab11a-exosome formation