Yasuko Onuma and Shuji Takahashi contributed equally to this work.
Xnr2 and Xnr5 unprocessed proteins inhibit Wnt signaling upstream of dishevelled
Article first published online: 28 SEP 2005
Copyright © 2005 Wiley-Liss, Inc.
Volume 234, Issue 4, pages 900–910, December 2005
How to Cite
Onuma, Y., Takahashi, S., Haramoto, Y., Tanegashima, K., Yokota, C., Whitman, M. and Asashima, M. (2005), Xnr2 and Xnr5 unprocessed proteins inhibit Wnt signaling upstream of dishevelled. Dev. Dyn., 234: 900–910. doi: 10.1002/dvdy.20574
- Issue published online: 16 NOV 2005
- Article first published online: 28 SEP 2005
- Manuscript Accepted: 4 AUG 2005
- Manuscript Revised: 16 JUL 2005
- Manuscript Received: 21 NOV 2004
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- International Cooperative Research Project (ICORP)
- Japan Science and Technology Agency (JST)
- TGF-β superfamily;
Nodal and Nodal-related proteins activate the Activin-like signal pathway and play a key role in the formation of mesoderm and endoderm in vertebrate development. Recent studies have shown additional activities of Nodal-related proteins apart from the canonical Activin-like signal pathway. Here we report a novel function of Nodal-related proteins using cleavage mutants of Xenopus nodal-related genes (cmXnr2 and cmXnr5), which are known to be dominant-negative inhibitors of nodal family signaling. cmXnr2 and cmXnr5 inhibited both BMP signaling and Wnt signaling without activating the Activin-like signal in animal cap assays. Pro region construct of Xnr2 and Xnr5 did not inhibit Xwnt8, and pro/mature region chimera mutant cmActivin-Xnr2 and cmActivin-Xnr5 also did not inhibit Xwnt8 activity. These results indicate that the pro domains of Xnr2 and Xnr5 are necessary, but not sufficient, for Wnt inhibition, by Xnr family proteins. In addition, Western blot analysis and immunohistochemistry analysis revealed that the unprocessed Xnr5 protein is stably produced and secreted as effectively as mature Xnr5 protein, and that the unprocessed Xnr5 protein diffused in the extracellular space. These results suggest that unprocessed Xnr2 and Xnr5 proteins may be involved in inhibiting both BMP and Wnt signaling and are able to be secreted to act on somewhat distant target cells, if these are highly produced. Developmental Dynamics 234:900–910, 2005. © 2005 Wiley-Liss, Inc.