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Bmper sticker sends Bmp to lysosomes

High levels of Bmper (green) inhibit Bmp (red) by triggering its internalization and degradation.

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

Kelley, R., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200808064.[Abstract/Free Full Text]

bshort{at}rockefeller.edu

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A concentration-dependent endocytic trap and sink mechanism converts Bmper from an activator to an inhibitor of Bmp signaling

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This Article Full Text (PDF, 1190K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Short, B. Search for Related Content PubMed Articles by Short, B. Related Collections Related Article Social Bookmarking                            What's this?