Robo and Ror function in a common receptor complex to regulate Wnt-mediated neurite outgrowth in Caenorhabditis elegans

Proceedings of the National Academy of Sciences of the United States of America
Jiaming Wang, Mei Ding

Abstract

Growing axons are exposed to various guidance cues en route to their targets, but the mechanisms that govern the response of growth cones to combinations of signals remain largely elusive. Here, we found that the sole Robo receptor, SAX-3, in Caenorhabditis elegans functions as a coreceptor for Wnt/CWN-2 molecules. SAX-3 binds to Wnt/CWN-2 and facilitates the membrane recruitment of CWN-2. SAX-3 forms a complex with the Ror/CAM-1 receptor and its downstream effector Dsh/DSH-1, promoting signal transduction from Wnt to Dsh. sax-3 functions in Wnt-responsive cells and the SAX-3 receptor is restricted to the side of the cell from which the neurite is extended. DSH-1 has a similar asymmetric distribution, which is disrupted by sax-3 mutation. Taking these results together, we propose that Robo receptor can function as a Wnt coreceptor to regulate Wnt-mediated biological processes in vivo.

References

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Citations

Jun 21, 2019·Therapeutic Advances in Medical Oncology·Zhengdong JiangZheng Wang
Dec 31, 2019·Current Opinion in Cell Biology·Janine Cravo, Sander van den Heuvel
May 16, 2021·Developmental Biology·Jacob I MardickDavid J Reiner
Jun 18, 2021·Frontiers in Cellular Neuroscience·Chang YinJay Z Parrish

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Methods Mentioned

BETA
nuclear translocation
two-hybrid
coimmunoprecipitation
co-IP
pull-down
pull down
transgenic
transfection
immunoprecipitation
Assay

Software Mentioned

ImageJ

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