Kelley et al. describe how a protein called Bmper switches off Bmp signaling by targeting the growth factor to lysosomes for degradation.

Many developmental processes are regulated by members of the Bmp family, and Bmp activity can be modulated by secreted binding partners. Bmper is one such modulator, but has the unusual ability of both enhancing and diminishing Bmp activity, depending on its concentration. Small amounts of Bmper promote Bmp signaling, whereas higher concentrations are inhibitory. How Bmper exerts these opposing effects was unclear.

Kelley et al. found that high concentrations of Bmper relative to Bmp prompted both proteins to be internalized and trafficked to lysosomes for destruction. The N terminus of Bmper trapped and inhibited Bmp at the cell surface, while the C terminus—along with the Bmp receptor—drove the complex's internalization. Lower concentrations of Bmper, in contrast, didn't induce Bmp uptake. The authors don't yet know what triggers the switch from activation to internalization, but think that saturated binding of Bmper might induce a structural change in either Bmp or its receptor.

Author Cam Patterson speculates that Bmper's dual role serves to temporally restrict Bmp signaling by initially activating the pathway before rapidly down-regulating it. Importantly, the team found that two other Bmp inhibitors also stimulated Bmp endocytosis, so Patterson thinks this new mechanism may represent a general method by which modulating proteins inhibit Bmp. BS

References

References
Kelley
R.
et al
.
2009
.
J. Cell Biol.
doi: .