Crossveinless-2 Is a BMP feedback inhibitor that binds Chordin/BMP to regulate Xenopus embryonic patterning.
Vertebrate Crossveinless-2 (CV2) is a secreted protein that can potentiate or antagonize BMP signaling. Through embryological and biochemical experiments we find that: (1) CV2 functions as a BMP4 feedback inhibitor in ventral regions of the Xenopus embryo; (2) CV2 complexes with Twisted gastrulation and BMP4; (3) CV2 is not a substrate for tolloid proteinases; (4) CV2 binds to purified Chordin protein with high affinity (K(D) in the 1 nM range); (5) CV2 binds even more strongly to Chordin proteolytic fragments resulting from Tolloid digestion or to full-length Chordin/BMP complexes; (6) CV2 depletion causes the Xenopus embryo to become hypersensitive to the anti-BMP effects of Chordin overexpression or tolloid inhibition. We propose that the CV2/Chordin interaction may help coordinate BMP diffusion to the ventral side of the embryo, ensuring that BMPs liberated from Chordin inhibition by tolloid proteolysis cause peak signaling levels.
Ambrosio
Andrea L
AL
Howard Hughes Medical Institute, Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Taelman
Vincent F
VF
Lee
Hojoon X
HX
Metzinger
Carrie A
CA
Coffinier
Catherine
C
De Robertis
E M
EM
D000818:Animals; D019521:Body Patterning; D055415:Bone Morphogenetic Protein 4; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000201:enzymology; D004843:Epistasis, Genetic; D025461:Feedback, Physiological; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D045726:Metalloproteases / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction; D055394:Tolloid-Like Metalloproteinases; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins / Q000378:metabolism*
C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011498:Protein Precursors; D011506:Proteins; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C517553:crossveinless 2 protein, mouse; C473561:twisted gastrulation protein, mouse; C054234:chordin; D052005:Bone Morphogenetic Protein Receptors, Type I; D045726:Metalloproteases; D055394:Tolloid-Like Metalloproteinases