PDZ interaction of Vangl2 links PSD-95 and Prickle2 but plays only a limited role in the synaptic localisation of Vangl2.
PDZ interaction of Vangl2 links PSD-95 and Prickle2 but plays only a limited role in the synaptic localisation of Vangl2.
复制标题
VANGL2的PDZ相互作用链接PSD-95和Prickle2，但在Vangl2的突触定位中起着有限的作用。
DOI：
10.1038/srep12916
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发表时间：
2015-08-10
影响因子：
4.6
通讯作者：
Kishi M
中科院分区：
文献类型：
--
作者：
Nagaoka T;Tabuchi K;Kishi M
突触后密度 95/圆盘大/小带闭塞-1 (PDZ) 结构域介导的蛋白质相互作用在各种分子生物学事件中发挥着关键作用，包括蛋白质定位、组装和信号转导。尽管平面细胞极性的脊椎动物调节因子 Van Gogh-like 2 (Vangl2) 最近被描述为具有 PDZ 结合基序的突触后分子，但其 PDZ 相互作用在突触中的作用尚不清楚。在本报告中，我们证明 PDZ 相互作用对于 Vangl2 的正常簇形成是可有可无的，并且对于培养的海马神经元中 Vangl2 的突触相关定位来说并不是绝对必需的。我们进一步表明，Vangl2 的突触定位分为两种类型：与突触后密度（PSD）-95 重叠共定位或与 PSD-95 高度相关但互补的关联模式。只有前者对 PDZ 结合基序的删除显着敏感。此外，PDZ 相互作用增强了 PSD-95 和 Prickle2 之间的蛋白质相互作用，Prickle2 是另一个位于突触后密度的平面细胞极性因子。结合我们最近的报告，即 Vangl2 沉默的神经元中 PSD-95 簇的密度降低，这些结果表明 Vangl2 决定了哺乳动物大脑中突触发生的突触后分子的复杂形成和聚集。
Postsynaptic density-95/Discs large/Zonula occludens-1 (PDZ) domain-mediated protein interactions play pivotal roles in various molecular biological events, including protein localisation, assembly, and signal transduction. Although the vertebrate regulator of planar cell polarity Van Gogh-like 2 (Vangl2) was recently described as a postsynaptic molecule with a PDZ-binding motif, the role of its PDZ interaction at the synapse is unknown. In this report, we demonstrate that the PDZ interaction was dispensable for the normal cluster formation of Vangl2 and not absolutely required for the synapse-associated localisation of Vangl2 in cultured hippocampal neurons. We further showed that the synaptic localisation of Vangl2 was categorised into two types: overlapping co-localisation with postsynaptic density (PSD)-95 or highly correlated but complementary pattern of association with PSD-95. Only the former was significantly sensitive to deletion of the PDZ-binding motif. In addition, the PDZ interaction enhanced the protein interactions between PSD-95 and Prickle2, which is another planar cell polarity factor that is localised at the postsynaptic density. Taken together with our recent report that the density of PSD-95 clusters was reduced in Vangl2-silenced neurons, these results suggest that Vangl2 determines the complex formation and clustering of postsynaptic molecules for synaptogenesis in mammalian brains.