Cited by 220Axon Guidance and Neuronal SignalingWnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene Regulation

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 +3 more·2007·Nature Cell Biology

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.

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Crossref · 10.1038/ncb1603

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  • PI3K/AKT, RAS/ERK, WNT and β-catenin pathways control soma size, dendritic arborization, axon generation, spine development and synapse function.

    “These pathways control soma size, dendritic arborization, axon generation, spine development and synapse function [184–188].”

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Authors
Zhang, X., Zhu, J., Yang, G.-Y., Wang, Q.-J., Qian, L., Chen, Y.-M., Chen, F., Tao, Y., Hu, H.-S., Wang, T., & Luo, Z.-G.
Affiliations
Chinese Academy of Sciences (CN)
Corresponding author
Luo, Zhen-Ge
Venue
Nature Cell Biology
Published
2007-06-10
Volume
9
Issue
7
Pages
743-754
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
OpenAlex
W2132289628
Cited by
220
References
43
Citations by year
2026: 1 · 2025: 5 · 2024: 8 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 14 · 2019: 7 · 2018: 10 · 2017: 6 · 2016: 6 · 2015: 12 · 2014: 11 · 2013: 19 · 2012: 16
FWCI
9.12
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
Dishevelled, atypical protein kinase C, Wnt5a, non-canonical Wnt signaling, hippocampal neurons, kinase activation, dominant negative kinase
MeSH terms
Wnt-5a Protein, Dishevelled Proteins, Protein Kinase C zeta, Animals, Axons, Carrier Proteins, Cells, Cultured, Dendrites, Embryo, Mammalian, Hippocampus, Nerve Tissue Proteins, Neurons, Phosphoproteins, Protein Kinase C, Signal Transduction, Cell Polarity, Adaptor Proteins, Signal Transducing, Wnt Proteins, Rats

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