PXD013480

PXD013480 is an original dataset announced via ProteomeXchange.

Title	WDFY2 restrains matrix metalloproteinase secretion and cell invasion by controlling VAMP3-dependent recycling
Description	The endosomal FYVE- and WD40-domain-containing protein WDFY2 has been assigned a function as tumor suppressor, but its functional mechanism has remained elusive. Here we have used confocal, widefield and super-resolution fluorescence microscopy to show that WDFY2 localizes to the base of retromer-containing endosomal tubules by a mechanism that involves recognition of highly curved membranes enriched in phosphatidylinositol 3-phosphate (PtdIns3P) by the WDFY2 FYVE domain. Affinity purification and mass spectrometry identified the v-SNARE VAMP3 as an interaction partner of WDFY2, and cellular knockout of WDFY2 caused a strong redistribution of VAMP3 into small vesicles near the plasma membrane. This was accompanied by VAMP3-dependent increased secretion of the matrix metalloproteinase MT1-MMP and enhanced degradation of extracellular matrix, and increased cell invasion. WDFY2 is frequently lost in metastatic cancers, most predominantly in ovarian and prostate cancer. We propose that WDFY2 acts as a tumor suppressor by serving as a gatekeeper for VAMP3 recycling.
HostingRepository	PRIDE
AnnounceDate	2019-07-02
AnnouncementXML	Submission_2019-07-03_00:18:39.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tuula Nyman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-12 03:10:40	ID requested
1	2019-07-02 06:12:20	announced
⏵ 2	2019-07-03 00:18:41	announced	Updated publication reference for PubMed record(s): 31253801.

Sneeggen M, Pedersen NM, Campsteijn C, Haugsten EM, Stenmark H, Schink KO, WDFY2 restrains matrix metalloproteinase secretion and cell invasion by controlling VAMP3-dependent recycling. Nat Commun, 10(1):2850(2019) [pubmed]

submitter keyword: WDFY2, VAMP3, endosome, PtdIns3P, recycling, cell invasion

Tuula Nyman
contact affiliation	Head of Proteomics
contact email	tuula.nyman@medisin.uio.no
lab head
Tuula Nyman
contact affiliation	University of Oslo
contact email	tuula.nyman@medisin.uio.no
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/2019/07/PXD013480

PRIDE project URI

• PRIDE
  1. PXD013480
     1. Label: PRIDE project
     2. Name: WDFY2 restrains matrix metalloproteinase secretion and cell invasion by controlling VAMP3-dependent recycling