Degradome of soluble ADAM10 and ADAM17 metalloproteases

Scharfenberg, Franka; Helbig, Andreas; Sammel, Martin; Benzel, Julia; Schlomann, Uwe; Peters, Florian; Wichert, Rielana; Bettendorff, Maximilian; Schmidt-Arras, Dirk; Rose-John, Stefan; Moali, Catherine; Lichtenthaler, Stefan F.; Pietrzik, Claus U.; Bartsch, Joerg W.; Tholey, Andreas und Becker-Pauly, Christoph (2020): Degradome of soluble ADAM10 and ADAM17 metalloproteases. In: Cellular and Molecular Life Sciences, Bd. 77, Nr. 2: S. 331-350

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198