The cell-tethered BMP binding protein Crossveinless 2 is a short-range co- receptor that promotes or inhibits BMP signaling in a concentration dependant manner

In Drosophila, the BMP binding protein Short gastrulation (Sog) both enhances and inhibits BMP activity in a spatially dependent manner, likely by facilitating transport of BMPs. In this report we examine the properties of a second Sog-like protein, Crossveinless 2 (Cv-2), and show that like Sog, it is a secreted BMP-binding protein that can either augment or inhibit BMP signaling. Unlike Sog however, this biphasic response is not mediated by BMP transport. Instead, using experimental and computational approaches, we demonstrate that Cv-2 acts locally to produce biphasic responses as a coreceptor. Whether Cv-2 enhances or inhibits signaling is dependent on a number of biophysical parameters including the relative binding affinities of receptors and Cv-2 to BMPs and the Cv-2 concentration. Since we find that Cv-2 expression is also under the control of BMP signaling, these combined properties enable Cv-2 to exquisitely tune BMP signaling in time and space.