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

Green, Jennifer L. and Inoue, Takao and Sternberg, Paul W. (2007) The C. Elegans ROR receptor tyrosine kinase, CAM-1, non-autonomously inhibits the Wnt pathway. Development, 134 (22). pp. 4053-4062. ISSN 0950-1991. doi:10.1242/dev.005363.

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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.

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Sternberg, Paul W.0000-0002-7699-0173
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.
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Thomas Hunt Morgan FellowshipUNSPECIFIED
Subject Keywords:ROR, CAM-1; Wnt; Vulva; Patterning; CRD; Organogenesis; Morphogen
Issue or Number:22
Record Number:CaltechAUTHORS:20100421-095202544
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Official Citation:Jennifer L. Green, Takao Inoue, and Paul W. Sternberg The C. elegans ROR receptor tyrosine kinase, CAM-1, non-autonomously inhibits the Wnt pathway Development 2007 134:4053-4062; published online before print October 17, 2007, doi:10.1242/dev.005363
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:18033
Deposited By: Jason Perez
Deposited On:21 Apr 2010 20:15
Last Modified:08 Nov 2021 23:40

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