Nagaoka Tadahiro, Tabuchi Katsuhiko, Kishi Masashi
Division of Cerebral Structure, Department of Cerebral Research, National Institute for Physiological Sciences, Okazaki 444-8787, Japan.
1] Division of Cerebral Structure, Department of Cerebral Research, National Institute for Physiological Sciences, Okazaki 444-8787, Japan [2] Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Sci Rep. 2015 Aug 10;5:12916. doi: 10.1038/srep12916.
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.
突触后致密蛋白95/盘状大蛋白/紧密连接蛋白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关键作用，包括蛋白质定位、组装和信号转导。尽管脊椎动物平面细胞极性调节因子类梵高蛋白2（Vangl2）最近被描述为一种具有PDZ结合基序的突触后分子，但其在突触处的PDZ相互作用的作用尚不清楚。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：与突触后致密物（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结合基序的缺失显著敏感。此外，PDZ相互作用增强了PSD-95与Prickle2之间的蛋白质相互作用，Prickle2是另一种定位于突触后致密物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形成的突触后分子的复合物形成和聚集。
