The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility

Maki Ishida-Takagishi, Atsushi Enomoto, Naoya Asai, Kaori Ushida, Takashi Watanabe, Takahiko Hashimoto, Takuya Kato, Liang Weng, Shinji Matsumoto, Masato Asai, Yoshiki Murakumo, Kozo Kaibuchi, Akira Kikuchi, Masahide Takahashi

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

Dishevelled is the common mediator of canonical and non-canonical Wnt signalling pathways, which are important for embryonic development, tissue maintenance and cancer progression. In the non-canonical Wnt signalling pathway, the Rho family of small GTPases acting downstream of Dishevelled has essential roles in cell migration. The mechanisms by which the non-canonical Wnt signalling pathway regulates Rac activation remain unknown. Here we show that Daple (Dishevelled-associating protein with a high frequency of leucine residues) regulates Wnt5a-mediated activation of Rac and formation of lamellipodia through interaction with Dishevelled. Daple increases the association of Dishevelled with an isoform of atypical protein kinase C, consequently promoting Rac activation. Accordingly, Daple deficiency impairs migration of fibroblasts and epithelial cells during wound healing in vivo. These findings indicate that Daple interacts with Dishevelled to direct the Dishevelled/protein kinase λ protein complex to activate Rac, which in turn mediates the non-canonical Wnt signalling pathway required for cell migration.

Original languageEnglish
Article number859
JournalNature communications
Volume3
DOIs
Publication statusPublished - 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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