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

ABSTRACT: 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].

SUBMITTER: Piccolo S

PROVIDER: S-EPMC3070600 | biostudies-literature | 1997 Oct

REPOSITORIES: biostudies-literature

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

Piccolo S S Agius E E Lu B B Goodman S S Dale L L De Robertis E M EM

Cell 19971001 3

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 dominan ...[more]

PMID: 9363949

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Self-regulation of the head-inducing properties of the Spemann organizer.

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The Spemann organizer gene, Goosecoid, promotes tumor metastasis.

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An ancient chordin-like gene in organizer formation of Hydra.

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Embryonic regeneration by relocalization of the Spemann organizer during twinning in Xenopus.

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Intramembrane proteolytic cleavage of a membrane-tethered transcription factor by a metalloprotease depends on ATP.

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