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 f ound to cleave Chordin and Chordin/ BMP-4 complexes at two specific si tes in biochemical experiments. Xolloid mRNA blocks secondary axes cau sed by chordin, but not by noggin, follistatin, or dominant-negative B MP receptor, mRNA injection. Xolloid-treated Chordin protein was unabl e to antagonize BMP activity. Furthermore, Xolloid digestion released biologically active BMPs from Chordin/BMP inactive complexes. Injectio n of dominant-negative Xolloid mRNA indicated that the in vivo functio n of Xolloid is to limit the extent of Spemann's organizer field. We p ropose that Xolloid regulates organizer function by a novel proteolyti c mechanism involving a double inhibition pathway required to pattern the dorsoventral axis: XOLL inverted left perpendicular CHD inverted i nverted perpendicular BMPs --> BMPR.