TY - JOUR
T1 - The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility
AU - Ishida-Takagishi, Maki
AU - Enomoto, Atsushi
AU - Asai, Naoya
AU - Ushida, Kaori
AU - Watanabe, Takashi
AU - Hashimoto, Takahiko
AU - Kato, Takuya
AU - Weng, Liang
AU - Matsumoto, Shinji
AU - Asai, Masato
AU - Murakumo, Yoshiki
AU - Kaibuchi, Kozo
AU - Kikuchi, Akira
AU - Takahashi, Masahide
N1 - Funding Information:
Formation of the Daple–Dvl–PKCλ tertiary complex was supported by additional GST (glutathione S-transferase) pull-down assays. The results showed that Daple CT, but not the Daple CT∆GCV mutant, interacted with PKCλ (Fig. 3e). This was consistent with our previous finding that Daple bound to the PDZ domain, but not other domains of Dvl30, suggesting that Daple formed a signalling complex with PKCλ that bound to the DEP domain of Dvl26. These data indicated that Daple binding to Dvl is essential for stable formation of the Dvl/PKCλ protein complex to subsequently
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms1861
DO - 10.1038/ncomms1861
M3 - Article
C2 - 22643886
AN - SCOPUS:84866356918
SN - 2041-1723
VL - 3
JO - Nature communications
JF - Nature communications
M1 - 859
ER -
