Dishevelled promotes axon differentiation by regulating atypical protein kinase C

• 作 者: XianZHANG;TongWANG;Zhen-GeLUO;JiZHU;Guo-YingYANG;Qing-JieWANG;LeiQIAN;Yan-MinCHEN;FeiCHEN;YuTAO;Han-SongHU;
• 机 构: Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institute for Biological Scie
• 出 处: 中国神经科学学会第四次会员代表大会暨第七届全国学术会议(The 7th Biennial Meeting and the
• 发表日期: 2007年期

　　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 diferenfiation,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,WntSa,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.