Abstract
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor (TGF)beta superfamily of ligands that regulate many crucial aspects of embryonic development and organogenesis. Unlike other TGFbeta ligands, co-receptors for BMP ligands have not been described. Here we show that DRAGON, a glycosylphosphatidylinositol-anchored member of the repulsive guidance molecule family, which is expressed early in the developing nervous system, enhances BMP but not TGFbeta signaling. DRAGON binds directly to BMP2 and BMP4 but not to BMP7 or other TGFbeta ligands. The enhancing action of DRAGON on BMP signaling is also reduced by administration of Noggin, a soluble BMP antagonist, indicating that the action of DRAGON is ligand-dependent. DRAGON associates directly with BMP type I (ALK2, ALK3, and ALK6) and type II (ActRII and ActRIIB) receptors, and its signaling is reduced by dominant negative Smad1 and ALK3 or -6 receptors. In the Xenopus embryo, DRAGON both reduces the threshold of the ability of Smad1 to induce mesodermal and endodermal markers and alters neuronal and neural crest patterning. The direct interaction of DRAGON with BMP ligands and receptors indicates that it is a BMP co-receptor that potentiates BMP signaling.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Body Patterning
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Bone Morphogenetic Protein Receptors
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / metabolism*
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Carrier Proteins
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Embryo, Mammalian / anatomy & histology
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Embryo, Mammalian / physiology
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Embryo, Nonmammalian
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Female
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Genes, Reporter
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Humans
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Mice
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Morphogenesis / physiology
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nervous System / anatomy & histology
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Nervous System / embryology
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Neural Cell Adhesion Molecules / genetics
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Neural Cell Adhesion Molecules / metabolism*
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Protein Binding
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Proteins / metabolism
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Receptors, Growth Factor / genetics
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Receptors, Growth Factor / metabolism
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Signal Transduction / physiology*
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Smad Proteins
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Smad1 Protein
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transforming Growth Factor beta / metabolism
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Xenopus Proteins
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Xenopus laevis / embryology
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Xenopus laevis / metabolism
Substances
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Bone Morphogenetic Proteins
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Carrier Proteins
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DNA-Binding Proteins
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DRAGON protein, mouse
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MXD1 protein, Xenopus
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Nerve Tissue Proteins
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Neural Cell Adhesion Molecules
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Protein Isoforms
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Proteins
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Receptors, Growth Factor
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SMAD1 protein, human
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Smad Proteins
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Smad1 Protein
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Smad1 protein, mouse
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Trans-Activators
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Transforming Growth Factor beta
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Xenopus Proteins
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noggin protein
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Bone Morphogenetic Protein Receptors