Mammalian Ryk Is a Wnt Coreceptor Required for Stimulation of Neurite Outgrowth
Abstract
The Ryk receptor belongs to the atypical receptor tyrosine kinase family. It is a new member of the family of Wnt receptor proteins. However, the molecular mechanisms by which the Ryk receptor functions remain unknown. Here, we report that mammalian Ryk, unlike the Drosophila Ryk homolog Derailed, functions as a coreceptor along with Frizzled for Wnt ligands. Ryk also binds to Dishevelled, through which it activates the canonical Wnt pathway, providing a link between Wnt and Dishevelled. Transgenic mice expressing Ryk siRNA exhibit defects in axon guidance, and Ryk is required for neurite outgrowth induced by Wnt-3a and in the activation of T cell factor (TCF) induced by Wnt-1. Thus, Ryk appears to play a crucial role in Wnt-mediated signaling.
Additional Information
© 2004 Cell Press. Under an Elsevier user license. Received 1 April 2004, Revised 16 September 2004, Accepted 16 September 2004, Available online 30 September 2004. We are especially grateful to Thea Lu for her technical assistance. We are in debt to Xi He, Raymond Habas, Martin Garcia Castro, Leonard Zon and Bert Vogelstein for reagents, to Susan Ou for generation of the mouse anti-Ryk serum, to Shirley Pease, Jennifer Alex and Bruce Kennedy for generation and maintenance of transgenic mice. We thank Kai Zinn, Chunming Liu, Raad Nashmi, Qiang Lu, Yosuke Mukoyama, Michiline Laurant and members of the Baltimore lab for reading this manuscript. This work was supported by NIH grant 2R01CA51462-13 (to D.B.) and Baxter Foundation (to W.L.).Attached Files
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Additional details
- Eprint ID
- 102724
- Resolver ID
- CaltechAUTHORS:20200422-150958391
- NIH
- 2R01CA51462-13
- Baxter Foundation
- Created
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2020-04-23Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field