Metalloprotease meprin beta generates nontoxic N-terminal amyloid precursor protein fragments in vivo.

ABSTRACT: Identification of physiologically relevant substrates is still the most challenging part in protease research for understanding the biological activity of these enzymes. The zinc-dependent metalloprotease meprin β is known to be expressed in many tissues with functions in health and disease. Here, we demonstrate unique interactions between meprin β and the amyloid precursor protein (APP). Although APP is intensively studied as a ubiquitously expressed cell surface protein, which is involved in Alzheimer disease, its precise physiological role and relevance remain elusive. Based on a novel proteomics technique termed terminal amine isotopic labeling of substrates (TAILS), APP was identified as a substrate for meprin β. Processing of APP by meprin β was subsequently validated using in vitro

SUBMITTER: Jefferson T 

PROVIDER: S-EPMC3149364 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature