Universität zu Köln

Lueckstaedt, Wiebke, Bub, Simon, Koudelka, Tomas, Pavlenko, Egor ORCID: 0000-0003-0293-052X, Peters, Florian ORCID: 0000-0002-8529-2326, Somasundaram, Prasath, Becker-Pauly, Christoph, Lucius, Ralph, Zunke, Friederike and Arnold, Philipp (2021). Cell Surface Processing of CD109 by Meprin beta Leads to the Release of Soluble Fragments and Reduced Expression on Extracellular Vesicles. Front. Cell. Dev. Biol., 9. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2296-634X

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Abstract

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 TGF beta, JAK-STAT3, YAP/TAZ, and EGFR/AKT/mTOR pathways. Here, we identify the metalloproteinase meprin beta 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 beta 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 beta 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lueckstaedt, Wiebke UNSPECIFIED UNSPECIFIED UNSPECIFIED Bub, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Koudelka, Tomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Pavlenko, Egor UNSPECIFIED orcid.org/0000-0003-0293-052X UNSPECIFIED Peters, Florian UNSPECIFIED orcid.org/0000-0002-8529-2326 UNSPECIFIED Somasundaram, Prasath UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker-Pauly, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Lucius, Ralph UNSPECIFIED UNSPECIFIED UNSPECIFIED Zunke, Friederike UNSPECIFIED UNSPECIFIED UNSPECIFIED Arnold, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-586224
DOI:	10.3389/fcell.2021.622390
Journal or Publication Title:	Front. Cell. Dev. Biol.
Volume:	9
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	2296-634X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language METALLOPROTEASE MEPRIN; PROTEOLYTIC CONTROL; ALPHA-SUBUNIT; COMPLEMENT; COMPONENT; IDENTIFICATION; GENE; CARCINOMA; PROMOTES; ABILITY Multiple languages Cell Biology; Developmental Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58622