Crossveinless-2 Is a BMP Feedback Inhibitor that Binds Chordin/BMP to Regulate Xenopus Embryonic Patterning

Andrea L. Ambrosio; Vincent F. Taelman; Hojoon Lee; Carrie A. Metzinger; Catherine Coffinier; E. M. De Robertis

doi:10.1016/j.devcel.2008.06.013

Crossveinless-2 Is a BMP Feedback Inhibitor that Binds Chordin/BMP to Regulate Xenopus Embryonic Patterning

Andrea L. Ambrosio, Vincent F. Taelman, Hojoon Lee, Carrie A. Metzinger, Catherine Coffinier, E. M. De Robertis^*

^*Corresponding author for this work

Neurobiology

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	248-260
Number of pages	13
Journal	Developmental Cell
Volume	15
Issue number	2
DOIs	https://doi.org/10.1016/j.devcel.2008.06.013
State	Published - Aug 12 2008

Funding

We thank members of our laboratory for comments on the manuscript; N. Ketpura, A. Mays, and C. Zer for help with preliminary studies and M. O'Connor and S. Blair for sharing results before publication. D. Geissert and T. Boe provided expert technical assistance. V.F.T. thanks C. Wylie and J. Heasman for help with the oocyte CV2 depletion experiment carried out at the Cold Spring Harbor Xenopus Embryology course. We are grateful to the UCLA core facility led by R. Lehrer for help with the Biacore analyses. This work was supported by NIH grant HD21502-22. E.M.D.R is an investigator of the Howard Hughes Medical Institute.

Keywords

DEVBIO
SIGNALING

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
Molecular Biology
Cell Biology
Developmental Biology

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10.1016/j.devcel.2008.06.013

Cite this

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title = "Crossveinless-2 Is a BMP Feedback Inhibitor that Binds Chordin/BMP to Regulate Xenopus Embryonic Patterning",

abstract = "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 (KD 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.",

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author = "Ambrosio, {Andrea L.} and Taelman, {Vincent F.} and Hojoon Lee and Metzinger, {Carrie A.} and Catherine Coffinier and {De Robertis}, {E. M.}",

note = "Funding Information: We thank members of our laboratory for comments on the manuscript; N. Ketpura, A. Mays, and C. Zer for help with preliminary studies and M. O'Connor and S. Blair for sharing results before publication. D. Geissert and T. Boe provided expert technical assistance. V.F.T. thanks C. Wylie and J. Heasman for help with the oocyte CV2 depletion experiment carried out at the Cold Spring Harbor Xenopus Embryology course. We are grateful to the UCLA core facility led by R. Lehrer for help with the Biacore analyses. This work was supported by NIH grant HD21502-22. E.M.D.R is an investigator of the Howard Hughes Medical Institute. ",

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AU - Ambrosio, Andrea L.

AU - Taelman, Vincent F.

AU - Lee, Hojoon

AU - Metzinger, Carrie A.

AU - Coffinier, Catherine

AU - De Robertis, E. M.

N1 - Funding Information: We thank members of our laboratory for comments on the manuscript; N. Ketpura, A. Mays, and C. Zer for help with preliminary studies and M. O'Connor and S. Blair for sharing results before publication. D. Geissert and T. Boe provided expert technical assistance. V.F.T. thanks C. Wylie and J. Heasman for help with the oocyte CV2 depletion experiment carried out at the Cold Spring Harbor Xenopus Embryology course. We are grateful to the UCLA core facility led by R. Lehrer for help with the Biacore analyses. This work was supported by NIH grant HD21502-22. E.M.D.R is an investigator of the Howard Hughes Medical Institute.

PY - 2008/8/12

Y1 - 2008/8/12

N2 - 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 (KD 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.

AB - 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 (KD 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.

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Crossveinless-2 Is a BMP Feedback Inhibitor that Binds Chordin/BMP to Regulate Xenopus Embryonic Patterning

Abstract

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Keywords

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