PXD023727

PXD023727 is an original dataset announced via ProteomeXchange.

Title	Cell surface processing of CD109 by meprin β leads to the release of soluble fragments and reduced expression on extracellular vesicles
Description	Cluster of differentiation 109 (CD109) is a glycosylphosphatidylinositol (GPI) anchored protein expressed on primitive hematopoietic stem cells, activated platelets, CD4+ and CD8+ T-cells and keratinocytes. In recent years CD109 was also associated with different tumor entities and identified as a possible future diagnostic marker linked to reduced patient survival. Also, different cell signaling pathways were proposed as targets for CD109 interference including the TGFβ, JAK-STAT3, YAP/TAZ and EGFR/AKT/mTOR pathways. Here, we identify the metalloproteinase meprin β to cleave CD109 at the cell surface and thereby induce the release of cleavage fragments of different size. Major cleavage was identified within the bait region of CD109 residing in the middle of the protein. To identify the structural localization of the bait region, homology modeling and single particle analysis were applied, resulting in a molecular model of membrane associated CD109, which allows for the localization of the newly identified cleavage sites for meprin β and the previously published cleavage sites for the metalloproteinase bone morphogenetic protein 1 (BMP-1). Full-length CD109 localized on extracellular vesicles (EVs) was also identified as a release mechanism and we can show that proteolytic cleavage of CD109 at the cell surface reduces the amount of CD109 sorted to EVs. In summary, we identified meprin β as the first membrane bound protease to cleave CD109 within the bait region, provide a first structural model for CD109 and show that cell surface proteolysis correlates negatively with CD109 released on EVs.
HostingRepository	PRIDE
AnnounceDate	2021-01-28
AnnouncementXML	Submission_2021-01-28_04:03:33.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tomas Koudelka
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	dimethylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-21 02:24:08	ID requested
⏵ 1	2021-01-28 04:03:34	announced

Dataset with its publication pending

submitter keyword: CD109

macroglobulin

meprin β

exosomes

extracellular vesicles

TEM

TEP1r

Pd. Philipp Arnold
contact affiliation	Institute of Functional and Clinical Anatomy, FAU Erlangen,91054 Erlangen, Germany
contact email	philipp.arnold@fau.de
lab head
Tomas Koudelka
contact affiliation	Institute for Experimental Medicine
contact email	t.koudelka@iem.uni-kiel.de
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/2021/01/PXD023727

PRIDE project URI

• PRIDE
  1. PXD023727
     1. Label: PRIDE project
     2. Name: Cell surface processing of CD109 by meprin β leads to the release of soluble fragments and reduced expression on extracellular vesicles