Dishevelled promotes axon differentiation by regulating atypical protein kinase C

Zhang, Xian, Zhu, Ji, Yang, Guo-Ying, Wang, Qing-Jie, Qian, Lei, Chen, Yan-Min, Chen, Fei, Tao, Yu, Hu, Han-Song, Wang, Tong and Luo, Zhen-Ge (2007) Dishevelled promotes axon differentiation by regulating atypical protein kinase C. Nature Cell Biology, 9 7: 743-U27. doi:10.1038/ncb1603

Author Zhang, Xian
Zhu, Ji
Yang, Guo-Ying
Wang, Qing-Jie
Qian, Lei
Chen, Yan-Min
Chen, Fei
Tao, Yu
Hu, Han-Song
Wang, Tong
Luo, Zhen-Ge
Title Dishevelled promotes axon differentiation by regulating atypical protein kinase C
Journal name Nature Cell Biology   Check publisher's open access policy
ISSN 1465-7392
Publication date 2007-07-01
Year available 2007
Sub-type Article (original research)
DOI 10.1038/ncb1603
Open Access Status Not yet assessed
Volume 9
Issue 7
Start page 743
End page U27
Total pages 17
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
The atypical protein kinase C (aPKC) in complex with PAR3 and PAR6 is required for axon-dendrite differentiation, but the upstream factors responsible for regulating its activity are largely unknown. Here, we report that in cultured hippocampal neurons aPKC is directly regulated by Dishevelled (Dvl), an immediate downstream effector of Wnt. We found that downregulation of Dvl abrogated axon differentiation, whereas Dvl overexpression resulted in multiple axon formation. Interestingly, Dvl was associated with aPKC and this interaction resulted in aPKC stabilization and activation. Furthermore, the multiple axon formation resulting from Dvl overexpression was attenuated by expressing a dominant-negative aPKC in these neurons and overexpression of aPKC prevented the loss of axon caused by Dvl downregulation. Finally, Wnt5a, a noncanonical Wnt, activated aPKC and promoted axon differentiation. The Wnt5a effect on axon differentiation was attenuated by downregulating Dvl or inhibiting aPKC. Thus, Dvl-aPKC interaction can promote axon differentiation mediated by the PAR3-PAR6-aPKC complex.
Keyword Hippocampal Neuronal Polarity
Wnt Signaling Pathway
Cell Polarity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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