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: [formula in text].
Piccolo
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Howard Hughes Medical Institute, Department of Biological Chemistry, University of California, Los Angeles 90095-1662, USA.
Agius
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Lu
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Goodman
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Dale
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De Robertis
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EM
D000595:Amino Acid Sequence; D000818:Animals; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004475:Ectoderm; D006023:Glycoproteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008648:Mesoderm; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D012333:RNA, Messenger; D013379:Substrate Specificity; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins
D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C525822:bmp7.1 protein, Xenopus; C054234:chordin; D008666:Metalloendopeptidases; C109187:TLL2 protein, Xenopus