Journal Article

DZNE-2020-07331

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Degradome of soluble ADAM10 and ADAM17 metalloproteases.

Scharfenberg, F. (Corresponding author) ; Helbig, A. ; Sammel, M. ; Benzel, J. ; Schlomann, U. ; Peters, F. ; Wichert, R. ; Bettendorff, M. ; Schmidt-Arras, D. ; Rose-John, S. ; Moali, C. ; Lichtenthaler, S. F.DZNE* ; Pietrzik, C. U. ; Bartsch, J. W. ; Tholey, A. ; Becker-Pauly, C.

2019
Springer International Publishing AG Cham (ZG)

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Please use a persistent id in citations: doi:10.1007/s00018-019-03184-4

Abstract: Disintegrin and metalloproteinases (ADAMs) 10 and 17 can release the extracellular part of a variety of membrane-bound proteins via ectodomain shedding important for many biological functions. So far, substrate identification focused exclusively on membrane-anchored ADAM10 and ADAM17. However, besides known shedding of ADAM10, we identified ADAM8 as a protease capable of releasing the ADAM17 ectodomain. Therefore, we investigated whether the soluble ectodomains of ADAM10/17 (sADAM10/17) exhibit an altered substrate spectrum compared to their membrane-bound counterparts. A mass spectrometry-based N-terminomics approach identified 134 protein cleavage events in total and 45 common substrates for sADAM10/17 within the secretome of murine cardiomyocytes. Analysis of these cleavage sites confirmed previously identified amino acid preferences. Further in vitro studies verified fibronectin, cystatin C, sN-cadherin, PCPE-1 as well as sAPP as direct substrates of sADAM10 and/or sADAM17. Overall, we present the first degradome study for sADAM10/17, thereby introducing a new mode of proteolytic activity within the protease web.

Keyword(s): ADAM10 Protein: metabolism (MeSH) ; ADAM17 Protein: metabolism (MeSH) ; Amino Acids: metabolism (MeSH) ; Amyloid Precursor Protein Secretases: metabolism (MeSH) ; Animals (MeSH) ; Cell Line (MeSH) ; HEK293 Cells (MeSH) ; Humans (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Metalloproteases: metabolism (MeSH) ; Mice (MeSH) ; Myocytes, Cardiac: metabolism (MeSH)

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Contributing Institute(s):

1. Neuroproteomics (AG Lichtenthaler)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; SCOPUS ; Web of Science Core Collection

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