PSD-95 is required to sustain the molecular organization of the postsynaptic density.
PSD-95 is required to sustain the molecular organization of the postsynaptic density.
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DOI：
10.1523/jneurosci.5968-10.2011
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发表时间：
2011-04-27
期刊：
影响因子：
--
通讯作者：
Reese TS
中科院分区：
文献类型：
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作者：
Chen X;Nelson CD;Li X;Winters CA;Azzam R;Sousa AA;Leapman RD;Gainer H;Sheng M;Reese TS
PSD-95是一种膜相关鸟苷酸激酶（MAGUK），是兴奋性突触后密度（PSD）的主要支架蛋白，也是突触强度的有效调节剂。在这里，我们表明，PSD-95是在一个扩展的配置和定位成规则阵列的垂直细丝，接触谷氨酸受体和正交的水平元件分层内的PSD在大鼠海马棘突触深处。RNAi敲低PSD-95导致PSD材料的整个斑块的损失，并且EM断层扫描显示斑块损失与含有PSD-95的垂直细丝、与垂直细丝相关的水平元件和推定的AMPA的损失相关，但与NMDA受体类型结构无关。这些观察结果表明，由含有PSD-95的垂直细丝及其相关的水平元件构建的正交分子支架对于维持PSD的三维分子组织是必不可少的。我们的研究结果为理解PSD-95在PSD中的功能作用提供了结构基础。
PSD-95, a membrane-associated guanylate kinase (MAGUK), is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength. Here we show that PSD-95 is in an extended configuration and positioned into regular arrays of vertical filaments that contact both glutamate receptors and orthogonal horizontal elements layered deep inside the PSD in rat hippocampal spine synapses. RNAi knockdown of PSD-95 leads to loss of entire patches of PSD material, and EM tomography shows that the patchy loss correlates with loss of PSD-95-containing vertical filaments, horizontal elements associated with the vertical filaments, and putative AMPA, but not NMDA receptor type structures. These observations show that the orthogonal molecular scaffold constructed from PSD-95-containing vertical filaments and their associated horizontal elements is essential for sustaining the three dimensional molecular organization of the PSD. Our findings provide a structural basis for understanding the functional role of PSD-95 at the PSD.