Collaborative Research Centre 877

Proteolysis as a Regulatory Event in Pathophysiology

Christian-Albrechts-Universität zu Kiel

Third Funding Period (2018-2022)

Project A13: Structural and functional properties of meprin metalloproteases with regard to cell signaling


Project (A13) Arnold deals with the structural properties of meprin proteases and their role as shedding en­zymes. It has been shown that the amyloid precursor protein can be cleaved at the β-secretase site by mem­brane bound meprin β, but not by soluble meprin α. The IL-6 receptor, however, can also be cleaved from the cell surface by membrane bound meprin β and additionally by soluble meprin α. The cell adhesion and trans­mem­brane signaling molecule β1 integrin can be cleaved by membrane bound and soluble meprin β, but not by meprin α. Since meprin α and meprin β exhibit similar cleavage specificities, but do not share all substrates, the existence of exo­sites might be involved in substrate recognition. The project will identify and target exo­sites within meprin α and meprin β and analyze functional consequences of meprin β overexpression in vivo with regard to β1 integrin signaling.