SUMOylation regulates kainate-receptor-mediated synaptic transmission.
SUMOylation regulates kainate-receptor-mediated synaptic transmission.
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DOI：
10.1038/nature05736
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发表时间：
2007-05-17
期刊：
影响因子：
64.8
通讯作者：
Henley, Jeremy M.
中科院分区：
文献类型：
--
作者：
Martin, Stephane;Nishimune, Atsushi;Mellor, Jack R.;Henley, Jeremy M.
小泛素样修饰蛋白 (SUMO) 调节转录活性和蛋白质跨核膜的易位。核外 SUMO 底物的鉴定正在取得进展，但人们对蛋白质 SUMO 化更广泛的细胞作用知之甚少。在这里，我们报告在大鼠海马神经元中，突触处存在多个 SUMO 化靶标，并且我们表明红藻氨酸受体亚基 GluR6 是 SUMO 底物。 GluR6 的 SUMO 化可调节红藻氨酸受体的内吞作用并改变突触传递。 GluR6 在静息条件下表现出低水平的 SUMO 化，并且响应红藻氨酸但不响应 N-甲基-D-天冬氨酸 (NMDA) 处理而快速 SUMO 化。使用 SUMO 特异性肽酶 SENP-1 减少 GluR6 SUMO 化可防止红藻氨酸诱发的红藻氨酸受体内吞作用。此外，突变的非 SUMOylatable 形式的 GluR6 不会响应 COS-7 细胞中的红藻氨酸而被内吞。与此一致的是，海马切片中的电生理记录表明红藻氨酸受体介导的兴奋性突触后电流因 SUMO 化而减少，并因去 SUMO 化而增强。这些数据揭示了 SUMO 在突触功能调节中的先前未被怀疑的作用。
The small ubiqwitin-like modifier protein (SUMO) regulates transcriptional activity and the translocation of proteins across the nuclear membrane. The identification of SUMO substrates outside the nucleus is progressing but little is yet known about the wider cellular role of protein SUMOylation. Here we report that in rat hippocampal neurons multiple SUMOylation targets are present at synapses and we show that the kainate receptor subunit GluR6 is a SUMO substrate. SUMOylation of GluR6 regulates endocytosis of the kainate receptor and modifies synaptic transmission. GluR6 exhibits low levels of SUMOylation under resting conditions and is rapidly SUMOylated in response to a kainate but not an N-methyl-D-aspartate (NMDA) treatment. Reducing GluR6 SUMOylation using the SUMO-specific isopeptidase SENP-1 prevents kainate-evoked endocytosis of the kainate receptor. Furthermore, a mutated non-SUMOylatable form of GluR6 is not endocytosed in response to kainate in COS-7 cells. Consistent with this, electrophysiological recordings in hippocampal slices demonstrate that kainate-receptor-mediated excitatory postsynaptic currents are decreased by SUMOylation and enhanced by deSUMOylation. These data reveal a previously unsuspected role for SUMO in the regulation of synaptic function.
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.0337412100
发表时间：
2003-02-04
影响因子：
11.1
作者：
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通讯作者：
Taylor, CT