The BMP-binding protein Crossveinless 2 is a short-range, concentration-dependent, biphasic modulator of BMP signaling in Drosophila.
In Drosophila, the secreted BMP-binding protein Short gastrulation (Sog) inhibits signaling by sequestering BMPs from receptors, but enhances signaling by transporting BMPs through tissues. We show that Crossveinless 2 (Cv-2) is also a secreted BMP-binding protein that enhances or inhibits BMP signaling. Unlike Sog, however, Cv-2 does not promote signaling by transporting BMPs. Rather, Cv-2 binds cell surfaces and heparan sulfate proteoglygans and acts over a short range. Cv-2 binds the type I BMP receptor Thickveins (Tkv), and we demonstrate how the exchange of BMPs between Cv-2 and receptor can produce the observed biphasic response to Cv-2 concentration, where low levels promote and high levels inhibit signaling. Importantly, we show also how the concentration or type of BMP present can determine whether Cv-2 promotes or inhibits signaling. We also find that Cv-2 expression is controlled by BMP signaling, and these combined properties enable Cv-2 to exquisitely tune BMP signaling.
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Mihaela
M
Serpe
David
D
Umulis
Amy
A
Ralston
Jun
J
Chen
David J
DJ
Olson
Andrei
A
Avanesov
Hans
H
Othmer
Michael B
MB
O'Connor
Seth S
SS
Blair
D000483:Alleles; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D019295:Computational Biology; D004220:Disulfides / Q000737:chemistry; D004330:Drosophila / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D008954:Models, Biological; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014921:Wings, Animal / Q000033:anatomy & histology / Q000196:embryology
D019485:Bone Morphogenetic Proteins; D004220:Disulfides; D029721:Drosophila Proteins; D019812:Heparan Sulfate Proteoglycans; D016212:Transforming Growth Factor beta; C415644:cv-2 protein, Drosophila; C064196:dpp protein, Drosophila; C089440:gbb protein, Drosophila