Chordin-mediated regulation of bone morphogenetic protein (BMP) family growth factors is essential in early embryogenesis and adult homoeostasis. Chordin binds to BMPs through cysteine-rich von Willebrand factor type C (vWC) homology domains and blocks them from interacting with their cell surface receptors. These domains also self-associate and enable chordin to target related proteins to fine-tune BMP regulation. The chordin–BMP inhibitory complex is strengthened by the secreted glycoprotein twisted gastrulation (Tsg); however, inhibition is relieved by cleavage of chordin at two specific sites by tolloid family metalloproteases. As Tsg enhances this cleavage process, it serves a dual role as both promoter and inhibitor of BMP signalling. Recent developments in chordin research suggest that rather than simply being by-products, the cleavage fragments of chordin continue to play a role in BMP regulation. In particular, chordin cleavage at the C-terminus potentiates its anti-BMP activity in a type-specific manner.
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October 2015
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Review Article|
October 09 2015
The role of chordin fragments generated by partial tolloid cleavage in regulating BMP activity
Helen Troilo;
Helen Troilo
*Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
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Anne L. Barrett;
Anne L. Barrett
*Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
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Alexander P. Wohl;
Alexander P. Wohl
†Center for Biochemistry, Medical Faculty, University of Cologne, D50931 Cologne, Germany
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Thomas A. Jowitt;
Thomas A. Jowitt
*Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
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Richard F. Collins;
Richard F. Collins
*Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
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Christopher P. Bayley;
Christopher P. Bayley
*Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
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Alexandra V. Zuk;
Alexandra V. Zuk
†Center for Biochemistry, Medical Faculty, University of Cologne, D50931 Cologne, Germany
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Gerhard Sengle;
Gerhard Sengle
†Center for Biochemistry, Medical Faculty, University of Cologne, D50931 Cologne, Germany
‡Center for Molecular Medicine Cologne, University of Cologne, D50931 Cologne, Germany
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Clair Baldock
Clair Baldock
1
*Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
1To whom correspondence should be addressed (emailclair.baldock@manchester.ac.uk).
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Publisher: Portland Press Ltd
Received:
April 16 2015
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2015 Authors; published by Portland Press Limited
2015
Biochem Soc Trans (2015) 43 (5): 795–800.
Article history
Received:
April 16 2015
Citation
Helen Troilo, Anne L. Barrett, Alexander P. Wohl, Thomas A. Jowitt, Richard F. Collins, Christopher P. Bayley, Alexandra V. Zuk, Gerhard Sengle, Clair Baldock; The role of chordin fragments generated by partial tolloid cleavage in regulating BMP activity. Biochem Soc Trans 1 October 2015; 43 (5): 795–800. doi: https://doi.org/10.1042/BST20150071
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