Vangl2 promotes Wnt/planar cell polarity-like signaling by antagonizing Dvl1-mediated feedback inhibition in growth cone guidance.
Vangl2 promotes Wnt/planar cell polarity-like signaling by antagonizing Dvl1-mediated feedback inhibition in growth cone guidance.
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DOI：
10.1016/j.devcel.2011.01.002
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发表时间：
2011-02-15
影响因子：
11.8
通讯作者：
Zou, Yimin
中科院分区：
文献类型：
--
作者：
Shafer, Beth;Onishi, Keisuke;Lo, Charles;Colakoglu, Gulsen;Zou, Yimin
尽管越来越多的证据支持Wnt-Frizzleed信号控制从脊椎动物到蠕虫的轴突引导，但这是否以及如何由平面细胞极性(PCP)信号介导仍然难以捉摸。我们在这里表明，核心的PCP组件是Wnt5a刺激的生长和连合轴突的前后引导所必需的。Dishevelled1可以通过增加Frizzled3的过度磷酸化和阻止其内化来抑制PCP信号转导。Vangl2通过减少Frizzled3的磷酸化来拮抗这种作用，并促进内化。在连合轴突生长锥体中，Vangl2主要分布在质膜上，在丝状伪足的顶端和出现新的丝状伪足的膜片中高度富含。综上所述，我们认为Vangl2和Dvl1的拮抗作用(超过Frizzled3的过度磷酸化和内吞作用)允许丝状足尖的PCP信号局部锐化，以感知定向线索Wnts，最终导致生长锥体的转向。
Although growing body of evidence supports that Wnt-Frizzled signaling controls axon guidance from vertebrates to worms, whether and how this is mediated by planar cell polarity (PCP) signaling remains elusive. We show here that the core PCP components are required for Wnt5a-stimulated outgrowth and anterior-posterior guidance of commissural axons. Dishevelled1 can inhibit PCP signaling by increasing hyperphosphorylation of Frizzled3 and preventing its internalization. Vangl2 antagonizes that by reducing Frizzled3 phosphorylation and promotes internalization. In commissural axon growth cones, Vangl2 is predominantly localized on the plasma membrane and is highly enriched on the tips of the filopodia as well as in patches of membrane where new filopodia emerge. Taken together, we propose that the antagonistic functions of Vangl2 and Dvl1 (over Frizzled3 hyperphosphorylation and endocytosis) allows sharpening of PCP signaling locally on the tips of the filopodia for sensing directional cues, Wnts, eventually causing turning of growth cones.
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