Dev. Cell 21, 375–383 (2011)

BMPs are secreted ligands that form concentration gradients across the dorsal-ventral (D/V) axis of developing tissues and thereby provide patterning information. Gradient formation is facilitated by modulators such as Chordin and Sog, homologous proteins that antagonize BMP signaling, or Tld, a metalloprotease responsible for signal degradation. Sog but not Chordin can also promote BMP diffusion; the biochemical foundation for this different biological activity is not understood. Now Peluso et al. demonstrate that BMP-dependent degradation of Sog but not Chordin could explain the difference. The authors identified three major Tld cleavage sites in Sog by sequencing degradation products; mutation of either of two sites retarded Sog degradation in vitro and mimicked Sog gain-of-function in Drosophila wing discs. Sog-i, a Sog variant with altered cleavage sites that can be cleaved independent of BMP, retained wild-type Sog-BMP interactions but decreased the net diffusive flux of BMP when expressed in wing discs. Sog-i expression broadened the spatial domain of active BMP signaling but resulted in a shallow-sloped concentration gradient, which resulted in cell fate changes along the D/V axis. Together these data indicate that residues in the Tld-recognition site render Sog cleavage dependent upon interaction with BMP, and that cosubstrate-dependent cleavage of Sog is important for BMP gradient formation and consequently D/V patterning.