The planar cell polarity protein Vangl2 bidirectionally regulates dendritic branching in cultured hippocampal neurons.
The planar cell polarity protein Vangl2 bidirectionally regulates dendritic branching in cultured hippocampal neurons.
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DOI：
10.1186/s13041-014-0079-5
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发表时间：
2014-11-12
期刊：
影响因子：
3.6
通讯作者：
Ohtsuka T
中科院分区：
文献类型：
--
作者：
Hagiwara A;Yasumura M;Hida Y;Inoue E;Ohtsuka T
Van Gogh-like (Vangl) 2 是一种平面细胞极性 (PCP) 蛋白，可调节动物发育过程中极化细胞和组织形态的诱导。在神经系统中，核心 PCP 信号蛋白已被确定可调节神经元成熟。在轴突生长锥中，PCP 成分的拮抗相互作用使丝状伪足的尖端对引导信号敏感。然而，PCP信号调节脊柱和树突发育的分子机制仍然不清楚。在这里，我们探索了以下发现：Vangl2 功能丧失会导致树突分支的树突棘密度和复杂性显着降低。尽管之前的报告显示，Vangl2 C 端 TSV 基序被证明是与 PSD-95 相互作用所必需的，并且 C 端细胞内结构域被证明与 N-钙粘蛋白相关，但缺失突变体（Vangl2-ΔTSV 和 Vangl2-ΔC）的过度表达对树突棘密度几乎没有影响。然而，当 N 末端区域缺失突变体过表达时，脊柱密度略有下调。有趣的是，缺失突变体对树突分支有更有效的影响，N端区域的缺失减少了树突分支，而C端区域的缺失则增加了树突分支。基于这些结果，Vangl2（PCP 信号通路的核心成分）似乎在神经复合体形成中具有功能性作用。特别是在树突分支的情况下，Vangl2 作为分子中枢在相反方向上调节神经形态。
Van Gogh-like (Vangl) 2 is a planar cell polarity (PCP) protein that regulates the induction of polarized cellular and tissue morphology during animal development. In the nervous system, the core PCP signaling proteins have been identified to regulate neuronal maturation. In axonal growth cones, the antagonistic interaction of PCP components makes the tips of filopodia sensitive to guidance cues. However, the molecular mechanism by which the PCP signaling regulates spine and dendritic development remains obscure. Here we explored the finding that a loss of function of Vangl2 results in a significant reduction in spine density and complexity of dendritic branching. In spite of a previous report, in which the Vangl2 C-terminal TSV motif was shown to be required for the interaction with PSD-95 and the C-terminal intracellular domain was shown to associate with N-cadherin, overexpression of deletion mutants (Vangl2-∆TSV and Vangl2-∆C) had little effect on spine density. However, when an N-terminal region deletion mutant was overexpressed, spine density was slightly down-regulated. Intriguingly, the deletion mutants had a more potent effect on dendritic branching, such that the deletion of the N-terminal region reduced dendritic branching, whereas deletion of the C-terminal region increased it. Based on these results, Vangl2, a core PCP signaling pathway component, appears to have a functional role in neural complex formation. Especially in the case of dendritic branching, Vangl2 serves as a molecular hub to regulate neural morphology in opposite directions.
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DOI：
10.1083/jcb.200307101
发表时间：
2004-01-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Takao-Rikitsu E;Mochida S;Inoue E;Deguchi-Tawarada M;Inoue M;Ohtsuka T;Takai Y
通讯作者：
Takai Y