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 and Masahide Takahashi ()
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Maki Ishida-Takagishi: Nagoya University Graduate School of Medicine
Atsushi Enomoto: Nagoya University Graduate School of Medicine
Naoya Asai: Nagoya University Graduate School of Medicine
Kaori Ushida: Nagoya University Graduate School of Medicine
Takashi Watanabe: Nagoya University Graduate School of Medicine
Takahiko Hashimoto: Nagoya University Graduate School of Medicine
Takuya Kato: Nagoya University Graduate School of Medicine
Liang Weng: Nagoya University Graduate School of Medicine
Shinji Matsumoto: Osaka University Graduate School of Medicine
Masato Asai: Nagoya University Graduate School of Medicine
Yoshiki Murakumo: Nagoya University Graduate School of Medicine
Kozo Kaibuchi: Nagoya University Graduate School of Medicine
Akira Kikuchi: Osaka University Graduate School of Medicine
Masahide Takahashi: Nagoya University Graduate School of Medicine

Nature Communications, 2012, vol. 3, issue 1, 1-12

Abstract: 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.

Date: 2012
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DOI: 10.1038/ncomms1861

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