A novel Wnt5a-Frizzled4 signaling pathway mediates activity-independent dendrite morphogenesis via the distal PDZ motif of Frizzled 4
A novel Wnt5a-Frizzled4 signaling pathway mediates activity-independent dendrite morphogenesis via the distal PDZ motif of Frizzled 4
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DOI：
10.1002/dneu.22250
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发表时间：
2015-08-01
影响因子：
3
通讯作者：
Yu, Xiang
中科院分区：
文献类型：
--
作者：
Bian, Wen-Jie;Miao, Wan-Ying;Yu, Xiang
树突状细胞的形态对神经元的功能和神经回路的连接至关重要。一些WNT家族成员已被证明在树枝晶发育中发挥重要作用。然而，负责调节这一过程的Wnt受体在很大程度上仍然难以捉摸。以原代培养的海马神经元为模型系统，我们报道了Wnt受体Fzd家族的成员Frizzled4(Fzd4)特异性地在Wnt5a下游发出信号来促进树突的分支和生长。有趣的是，Fzd4远端不太保守的PDZ结合基序，而不是其保守的近端DVL与PDZ相互作用的基序，是介导这一效应所必需的。我们进一步表明，DVL在促进树枝晶生长方面与FZD4平行且不依赖于FZD4。与大多数以前描述的途径不同，Wnt5a/Fzd4信号以一种活动无关和自分泌的方式促进树突的发育。综上所述，这些结果提供了第一个在哺乳动物系统中调节树突发育的Wnt受体，并证明了Fzd4远端PDZ基序在树突形态发生中的新功能，从而扩大了我们对Wnt信号在神经发育中复杂作用的认识。(C)2014 Wiley期刊，Inc.开发神经生物学75：805？822,2015
The morphology of the dendritic tree is critical to neuronal function and neural circuit wiring. Several Wnt family members have been demonstrated to play important roles in dendrite development. However, the Wnt receptors responsible for mediating this process remain largely elusive. Using primary hippocampal neuronal cultures as a model system, we report that Frizzled4 (Fzd4), a member of the Fzd family of Wnt receptors, specifically signals downstream of Wnt5a to promote dendrite branching and growth. Interestingly, the less conserved distal PDZ binding motif of Fzd4, and not its conserved proximal Dvl-interacting PDZ motif, is required for mediating this effect. We further showed that Dvl signaled parallel to and independent of Fzd4 in promoting dendrite growth. Unlike most previously described pathways, Wnt5a/Fzd4 signaling promoted dendrite development in an activity-independent and autocrine fashion. Together, these results provide the first identification of a Wnt receptor for regulating dendrite development in the mammalian system, and demonstrate a novel function of the distal PDZ motif of Fzd4 in dendrite morphogenesis, thereby expanding our knowledge of the complex roles of Wnt signaling in neural development. (c) 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 805?822, 2015