Cleavage of chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann organizer activity

The Xolloid secreted metalloprotease, a tolloid-related protein, was found to cleave Chordin and Chordin/ BMP-4 complexes at two specific sites in biochemical experiments. Xolloid mRNA blocks secondary axes caused by chordin, but not by noggin, follistatin, or dominant-negative BMP receptor, mRNA injection. Xolloid-treated Chordin protein was unable to antagonize BMP activity. Furthermore, Xolloid digestion released biologically active BMPs from Chordin/BMP inactive complexes. Injection of dominant-negative Xolloid mRNA indicated that the in vivo function of Xolloid is to limit the extent of Spemann's organizer field. We propose that Xolloid regulates organizer function by a novel proteolytic mechanism involving a double inhibition pathway required to pattern the dorsoventral axis: XOLL inverted left perpendicular CHD inverted inverted perpendicular BMPs --> BMPR.