title: The role of chordin fragments generated by partial tolloid cleavage in regulating BMP activity.
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.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
authors.forename: Helen
authors.initials: H
authors.lastname: Troilo
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Barrett
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, D50931 Cologne, Germany.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Wohl
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Jowitt
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Collins
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Bayley
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, D50931 Cologne, Germany.
authors.forename: Alexandra V
authors.initials: AV
authors.lastname: Zuk
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, D50931 Cologne, Germany Center for Molecular Medicine Cologne, University of Cologne, D50931 Cologne, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Sengle
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K. clair.baldock@manchester.ac.uk.
authors.forename: Clair
authors.initials: C
authors.lastname: Baldock
mesh_terms: D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction; D055394:Tolloid-Like Metalloproteinases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D011506:Proteins; C576635:TWSG1 protein, human; C054234:chordin; D052004:Bone Morphogenetic Protein Receptors; D055394:Tolloid-Like Metalloproteinases
keywords: bone morphogenetic protein (BMP) signalling; chordin; tolloid cleavage