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Published November 15, 2007 | Supplemental Material + Published
Journal Article Open

The C. Elegans ROR receptor tyrosine kinase, CAM-1, non-autonomously inhibits the Wnt pathway

Abstract

Inhibitors of Wnt signaling promote normal development and prevent cancer by restraining when and where the Wnt pathway is activated. ROR proteins, a class of Wnt-binding receptor tyrosine kinases, inhibit Wnt signaling by an unknown mechanism. To clarify how RORs inhibit the Wnt pathway, we examined the relationship between Wnts and the sole C. elegans ROR homolog, cam-1, during C. elegans vulval development, a Wnt-regulated process. We found that loss and overexpression of cam-1 causes reciprocal defects in Wnt-mediated cell-fate specification. Our molecular and genetic analyses revealed that the CAM-1 extracellular domain (ECD) is sufficient to non-autonomously antagonize multiple Wnts, suggesting that the CAM-1/ROR ECD sequesters Wnts. A sequestration model is supported by our findings that the CAM-1 ECD binds to several Wnts in vitro. These results demonstrate how ROR proteins help to refine the spatial pattern of Wnt activity in a complex multicellular environment.

Additional Information

© 2007 Company of Biologists. Accepted August 25, 2007. We thank Gladys Medina and Barbara Perry for technical assistance and members of the Sternberg laboratory for helpful discussions. For reagents and worms we thank W. Forrester, C. Wu, A. Fire, A. V. Maricq, M. Francis, D. Sherwood, I. Greenwald and H. Sawa. Some Nematode strains were from the Caenorhabditis Genetics Center, funded by the NIH National Center for Research Resources. We thank Cheryl Van Buskirk, Ryan Baugh, Jagan Srinivasan and Mihoko Kato for critically reading the manuscript; the Benzer laboratory (especially Gil Carvallo) for use of their microplate spectrophotometer; the Hay laboratory for use of their tissue culture hood; Jost Vielmetter and Inderjit Nangiana of the Caltech Protein Expression Facility for production of CRD-AP conditioned media; and Julie Gleason for kindly exchanging lin-17 and mom-5 mutant alleles. P.W.S. is an investigator with the Howard Hughes Medical Institute and J.L.G. was supported by the Thomas Hunt Morgan Fellowship for graduate study toward the doctor of philosophy degree in biology at the California Institute of Technology.

Attached Files

Published - GREdev07.pdf

Supplemental Material - DEV005363-FigS1.jpg

Supplemental Material - DEV005363tables_1-3.pdf

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Created:
August 22, 2023
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October 20, 2023