Sarah A Laurent, Franziska S Hoffmann, Peer-Hendrik Kuhn, Qingyu Cheng, Yuanyuan Chu, Marc Schmidt-Supprian, Stefanie M Hauck, Elisabeth Schuh, Markus Krumbholz, Heike Rübsamen, Johanna Wanngren, Mohsen Khademi, Tomas Olsson, Tobias Alexander, Falk Hiepe, Hans-Walter Pfister, Frank Weber, Dieter Jenne, Hartmut Wekerle, Reinhard Hohlfeld, Stefan F Lichtenthaler, Edgar Meinl
Survival of plasma cells is regulated by B-cell maturation antigen (BCMA), a membrane-bound receptor activated by its agonist ligands BAFF and APRIL. Here we report that γ-secretase directly cleaves BCMA, without prior truncation by another protease. This direct shedding is facilitated by the short length of BCMA's extracellular domain. In vitro, γ-secretase reduces BCMA-mediated NF-κB activation. In addition, γ-secretase releases soluble BCMA (sBCMA) that acts as a decoy neutralizing APRIL. In vivo, inhibition of γ-secretase enhances BCMA surface expression in plasma cells and increases their number in the bone marrow...
June 11, 2015: Nature Communications