Conformational change of Dishevelled plays a key regulatory role in the Wnt signaling pathways

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Abstract

The intracellular signaling molecule Dishevelled (Dvl) mediates canonical and non-canonical Wnt signaling via its PDZ domain. Different pathways diverge at this point by a mechanism that remains unclear. Here we show that the peptide-binding pocket of the Dvl PDZ domain can be occupied by Dvl's own highly conserved C-terminus, inducing a closed conformation. In Xenopus, Wnt-regulated convergent extension (CE) is readily affected by Dvl mutants unable to form the closed conformation than by wild-type Dvl. We also demonstrate that while Dvl cooperates with other Wnt pathway elements to activate canonical Wnt signaling, the open conformation of Dvl more effectively activates Jun N-terminal kinase (JNK). These results suggest that together with other players in the Wnt signaling pathway, the conformational change of Dvl regulates Wnt stimulated JNK activity in the non-canonical Wnt signaling.

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Ho-Jin Lee

Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, United States

Competing interests
The authors declare that no competing interests exist.
De-Li Shi

Laboratoire de biologie du développement, Institut de Biologie Paris-Seine, Sorbonne Universités, Paris, France

Competing interests
The authors declare that no competing interests exist.
Jie J Zheng

Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, United States

For correspondence
jzheng@jsei.ucla.edu

Competing interests
The authors declare that no competing interests exist.

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