Nat Neurosci：大脑神经细胞保护新视角

4月22日，国际著名杂志《自然—神经科学》Nature Neuroscience上刊登了国外研究人员的最新研究成果“SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity”，文章中，来自英国布里斯托尔大学的神经学家们在研究中发现了一种被称为SUMO的蛋白对减少或增强大脑神经细胞保护机制的化学过程起重要调控作用。这种关键蛋白在心力衰竭或癫痫发作过程中能够激活保护神经细胞免受损伤，并且它还调控大脑神经细胞间的信息传递。这项研究将有可能推动开发出中风和癫痫的治疗新策略。

研究人员证实这些关键的SUMO蛋白通过对大脑活动水平生成精细的反应而调控了红藻氨酸受体（Kainate receptor， KAR）传输的信号量。红藻氨酸受体对神经细胞间的沟通起重要作用，受体激活可导致癫痫发作和神经细胞死亡。

布里斯托尔大学医学院的Jack Mellor指出：“红藻氨酸受体是一组非常重要的蛋白，已知与包括癫痫在内的大量疾病有关。这些研究发现为我们提供了SUMO和红藻氨酸受体之间的联系，增进了我们对于神经细胞保护自身免于过度和不正常活动机制的理解。”（生物谷Bioon.com）

doi:10.1038/nn.3089
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SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity

Sophie E L Chamberlain, Inmaculada M González-González, Kevin A Wilkinson, Filip A Konopacki, Sriharsha Kantamneni, Jeremy M Henley & Jack R Mellor

Phosphorylation or SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. However, it is unknown whether phosphorylation and SUMOylation of GluK2 are important for activity-dependent KAR synaptic plasticity. We found that protein kinase C–mediated phosphorylation of GluK2 at serine 868 promotes GluK2 SUMOylation at lysine 886 and that both of these events are necessary for the internalization of GluK2-containing KARs that occurs during long-term depression of KAR-mediated synaptic transmission at rat hippocampal mossy fiber synapses. Conversely, phosphorylation of GluK2 at serine 868 in the absence of SUMOylation led to an increase in KAR surface expression by facilitating receptor recycling between endosomal compartments and the plasma membrane. Our results suggest a role for the dynamic control of synaptic SUMOylation in the regulation of KAR synaptic transmission and plasticity.