1. The role of chordin fragments generated by partial tolloid cleavage in regulating BMP activity.
- Author
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Troilo H, Barrett AL, Wohl AP, Jowitt TA, Collins RF, Bayley CP, Zuk AV, Sengle G, and Baldock C
- Subjects
- Animals, Bone Morphogenetic Protein Receptors agonists, Bone Morphogenetic Protein Receptors chemistry, Bone Morphogenetic Protein Receptors metabolism, Bone Morphogenetic Proteins chemistry, Bone Morphogenetic Proteins metabolism, Glycoproteins chemistry, Humans, Intercellular Signaling Peptides and Proteins chemistry, Peptide Fragments chemistry, Peptide Fragments metabolism, Protein Interaction Domains and Motifs, Protein Stability, Proteins chemistry, Proteolysis, Tolloid-Like Metalloproteinases chemistry, Bone Morphogenetic Protein Receptors antagonists & inhibitors, Bone Morphogenetic Proteins antagonists & inhibitors, Glycoproteins metabolism, Intercellular Signaling Peptides and Proteins metabolism, Models, Biological, Proteins metabolism, Signal Transduction, Tolloid-Like Metalloproteinases metabolism
- Abstract
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., (© 2015 Authors; published by Portland Press Limited.)
- Published
- 2015
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