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.
The role of chordin fragments generated by partial tolloid cleavage in regulating BMP activity
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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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