Dishevelled promotes axon differentiation by regulating atypical protein kinase C.
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.
Zhang
Xian
X
Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Zhu
Ji
J
Yang
Guo-Ying
GY
Wang
Qing-Jie
QJ
Qian
Lei
L
Chen
Yan-Min
YM
Chen
Fei
F
Tao
Yu
Y
Hu
Han-Song
HS
Wang
Tong
T
Luo
Zhen-Ge
ZG
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D000072261:Dishevelled Proteins; D004622:Embryo, Mammalian / Q000166:cytology; D006624:Hippocampus / Q000166:cytology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction; D051153:Wnt Proteins / Q000502:physiology*; D000071818:Wnt-5a Protein; D000099221:Protein Kinase C zeta
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D000072261:Dishevelled Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011493:Protein Kinase C; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D000099221:Protein Kinase C zeta; C472451:Pard3 protein, rat; C504908:Pard6a protein, rat; C491837:Wnt5a protein, rat