Anselm Sommer, Felix Kordowski, Joscha Büch, Thorsten Maretzky, Astrid Evers, Jörg Andrä, Stefan Düsterhöft, Matthias Michalek, Inken Lorenzen, Prasath Somasundaram, Andreas Tholey, Frank D Sönnichsen, Karl Kunzelmann, Lena Heinbockel, Christian Nehls, Thomas Gutsmann, Joachim Grötzinger, Sucharit Bhakdi, Karina Reiss
ADAM17, a prominent member of the 'Disintegrin and Metalloproteinase' (ADAM) family, controls vital cellular functions through cleavage of transmembrane substrates. Here we present evidence that surface exposure of phosphatidylserine (PS) is pivotal for ADAM17 to exert sheddase activity. PS exposure is tightly coupled to substrate shedding provoked by diverse ADAM17 activators. PS dependency is demonstrated in the following: (a) in Raji cells undergoing apoptosis; (b) in mutant PSA-3 cells with manipulatable PS content; and (c) in Scott syndrome lymphocytes genetically defunct in their capacity to externalize PS in response to intracellular Ca(2+) elevation...
2016: Nature Communications