First published online June 5, 2007
Journal of Cell Science 120, 1201e (2007)
© The Company of Biologists Limited
Epimorphin defies convention
Most secreted proteins exit cells via the ER and Golgi, following the `classical' secretory pathway. But some are delivered through much less well-defined, `non-classical' routes - one such molecule is the morphogen epimorphin. Epimorphin also has a known role in intracellular vesicle docking and fusion (it is a so-called `syntaxin'), but its secretion (and therefore its role as a morphogen) is controversial. Now, Yohei Hirai and colleagues (p. 2032) have defined the key regions of epimorphin responsible for this. By following secretion of epimorphin in mammary fibroblasts transfected with various mutant forms of the protein, they identified the domains required for its membrane translocation and a residue (His246) critical for its release. They also found that epimorphin associates with synaptotagmin and annexin II - both of which are involved in export of FGF1, another protein that takes a non-classical route. The authors then asked what happens to epimorphin after it is secreted. Using human mammary epithelial cells, they show that it binds to 
v-integrin-containing receptors, which have roles in morphogenesis as well as anti-apoptotic functions. This triggers downstream signalling pathways and the induction of epithelial morphogenesis.
Related articles in JCS:
- Non-classical export of epimorphin and its adhesion to v-integrin in regulation of epithelial morphogenesis
- Yohei Hirai, Celeste M. Nelson, Kyoko Yamazaki, Kyoko Takebe, Jennifer Przybylo, Benjamin Madden, and Derek C. Radisky
JCS 2007 120: 2032-2043.
[Abstract]
[Full Text]
