Wnt-3a and Dvl induce neurite retraction by activating Rho-associated kinase
Wnt-3a and Dvl induce neurite retraction by activating Rho-associated kinase
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DOI：
10.1128/mcb.24.10.4487-4501.2004
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发表时间：
2004-05-01
影响因子：
5.3
通讯作者：
Kikuchi, A
中科院分区：
文献类型：
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作者：
Kishida, S;Yamamoto, H;Kikuchi, A
DO是将Wnt信号传递到经典β-连环蛋白途径和非经典平面细胞极性（PCP）途径的关键蛋白。我们研究了Rho相关激酶（Rho-激酶）在哺乳动物细胞PCP途径中的作用，Rho-激酶被Dvl激活。DA-1、Wnt-1或Wnt-3a的表达激活COS细胞中的Rho激酶，并且这种激活被Rho激酶的Rho结合结构域抑制。Dvl-1在PC 12细胞中的表达激活Rho并抑制神经生长因子（NGF）诱导的神经突起生长。这种抑制作用被Rho激酶抑制剂逆转，但不能被c-Jun N-末端激酶抑制剂逆转。Dvl-1还抑制N1 E-115细胞的血清饥饿依赖性神经突生长，并且Rho激酶的Rho结合结构域的表达逆转了Dvl-1的这种抑制活性。不激活Rho激酶的Dvl-1突变体不抑制N1 E-115细胞的神经突生长。此外，纯化的Wnt-3a蛋白激活Rho激酶并抑制PC 12细胞的NGF依赖性神经突起生长。Wnt-3a依赖性神经突收缩也被Rho激酶抑制剂和抑制Wnt-3a依赖性Rho激酶激活的Dvl-1突变体阻止。这些结果表明Wnt-3a和Dvl通过Rho激酶调节神经突形成，并且PC 12和N1 E-115细胞可用于分析PCP途径。
DO is a key protein that transmits the Wnt signal to the canonical beta-catenin pathway and the noncanonical planar cell polarity (PCP) pathway. We studied the roles of Rho-associated kinase (Rho-kinase), which is activated by Dvl in the PCP pathway of mammalian cells. The expression of DA-1, Wnt-1, or Wnt-3a activated Rho-kinase in COS cells, and this activation was inhibited by the Rho-binding domain of Rho-kinase. The expression of Dvl-1 in PC12 cells activated Rho and inhibited nerve growth factor (NGF)-induced neurite outgrowth. This inhibition was reversed by a Rho-kinase inhibitor but not by a c-Jun N-terminal kinase inhibitor. Dvl-1 also inhibited serum starvation-dependent neurite outgrowth of N1E-115 cells, and expression of the Rho-binding domain of Rho-kinase reversed this inhibitory activity of Dvl-1. Dvl-1 mutants that did not activate Rho-kinase did not inhibit the neurite outgrowth of N1E-115 cells. Furthermore, the purified Wnt-3a protein activated Rho-kinase and inhibited the NGF-dependent neurite outgrowth of PC12 cells. Wnt-3a-dependent neurite retraction was also prevented by a Rho-kinase inhibitor and a Dvl-1 mutant that suppresses Wnt-3a-dependent activation of Rho-kinase. These results suggest that Wnt-3a and Dvl regulate neurite formation through Rho-kinase and that PC12 and N1E-115 cells are useful for analyzing the PCP pathway.