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

• Published in: Cell Vol. 91; no. 3; pp. 407 - 416
• Main Authors: Piccolo, S, Agius, E, Lu, B, Goodman, S, Dale, L, De Robertis, E M
• Format: Journal Article
• Language: English
• Published: United States 31-10-1997
• Subjects: Amino Acid Sequence; Animals; Bone Morphogenetic Protein 4; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins - metabolism; Ectoderm; Freshwater; Glycoproteins - metabolism; Intercellular Signaling Peptides and Proteins; Mesoderm; Metalloendopeptidases - metabolism; Molecular Sequence Data; RNA, Messenger; Substrate Specificity; Transforming Growth Factor beta; Xenopus; Xenopus Proteins
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/s0092-8674(00)80424-9

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: [formula in text].