I like the term repulsive guidance molecule. Ask your researcher to explain what the next steps are for using this in stroke therapy.
http://www.cell.com/developmental-cell/retrieve/pii/S1534580711005326- Highlights
- SKI-1 and Furin activate RGMa
- Membrane-bound and soluble RGMa control axonal growth
- Independent RGMa domains regulate axons through the same Neogenin domain
Summary
The nervous system is enormously complex, yet the number of cues that control axonal growth is surprisingly meager. Posttranslational modifications amplify diversity, but the degree to which they are employed is unclear. Here, we show that Furin and SKI-1 combine with autocatalytic cleavage and a disulfide bridge to generate four membrane-bound and three soluble forms of the
repulsive guidance molecule (RGMa). We provide in vivo evidence that these proprotein convertases are involved in axonal growth and that RGMa cleavage is essential for Neogenin-mediated outgrowth inhibition. Surprisingly, despite no sequence homology, N- and C-RGMa fragments bound the same Fibronectin-like domains in Neogenin and blocked outgrowth. This represents an example in which unrelated fragments from one molecule inhibit outgrowth through a single receptor domain. RGMa is a tethered membrane-bound molecule, and proteolytic processing amplifies RGMa diversity by creating soluble versions with long-range effects as well.
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