The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase.
The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase.
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DOI：
10.1016/j.devcel.2007.11.020
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发表时间：
2008-02
影响因子：
11.8
通讯作者：
Huaye Zhang;I. Macara
中科院分区：
文献类型：
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作者：
Huaye Zhang;I. Macara
大脑中的大部分兴奋性突触传递发生在树突棘，树突棘是树突上富含肌动蛋白的突起。这些结构的不对称性质表明调节细胞极性的蛋白质可能参与其形成。事实上，极性蛋白 PAR-3 是正常脊柱形态发生所必需的。然而，该功能与非典型蛋白激酶 C (aPKC) 和 PAR-6 无关。在这里，我们证明 PAR-6 与 aPKC 在脊柱形态发生中发挥着独特但重要的作用。 PAR-6 的敲低会抑制脊柱形态发生，而 PAR-6 的过度表达会增加脊柱密度，这些效应是由 aPKC 介导的。使用 FRET 生物传感器，我们进一步表明 p190 RhoGAP 和 RhoA 在 PAR-6/aPKC 复合物的下游发挥作用。这些结果定义了 PAR-6 和 aPKC 在树突棘生物发生和维持中的作用，并揭示了 PAR-6/aPKC 复合物与 RhoA 活性之间的意外联系。
The majority of excitatory synaptic transmission in the brain occurs at dendritic spines, which are actin-rich protrusions on the dendrites. The asymmetric nature of these structures suggests that proteins regulating cell polarity might be involved in their formation. Indeed, the polarity protein PAR-3 is required for normal spine morphogenesis. However, this function is independent of association with atypical protein kinase C (aPKC) and PAR-6. Here we show that PAR-6 together with aPKC plays a distinct but essential role in spine morphogenesis. Knockdown of PAR-6 inhibits spine morphogenesis, whereas overexpression of PAR-6 increases spine density, and these effects are mediated by aPKC. Using a FRET biosensor, we further show that p190 RhoGAP and RhoA act downstream of the PAR-6/aPKC complex. These results define a role for PAR-6 and aPKC in dendritic spine biogenesis and maintenance, and reveal an unexpected link between the PAR-6/aPKC complex and RhoA activity.