SUMOylation of the kainate receptor subunit GluK2 contributes to the activation of the MLK3-JNK3 pathway following kainate stimulation

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• 作者：Qiu-Ju Zhu^a ; ^b ; ^c ; Yan Xu^b ; ^c ; Cai-Ping Du^b ; ^c ; Xiao-Yu Hou^a ; ^b ; ^c ; ^{xyhou@xzmc.edu.cn}
• 关键词：AMPA ; 伪-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ; GluK2 ; glutamatergic kainate receptor subunit 2 ; JNK3 ; c-Jun N-terminal kinase 3 ; MAPK ; mitogen-activated protein kinases ; MLK3 ; mixed lineage kinase 3 ; NMDA ; N-methy-d-aspartate ; SUMO ; small ub
• 刊名：FEBS Letters
• 出版年：2012
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：7 May, 2012
• 卷：586
• 期：9
• 页码：1259-1264
• 文件大小：747 K

摘要

Protein SUMOylation has been implicated in the pathogenesis of ischemic stroke. However, the underlying mechanisms remain unclear. Here, we found that global brain ischemia evokes a sustained elevation of GluK2 SUMOylation in the rat hippocampal CA1 region. Over-expression of wild-type GluK2, but not SUMOylation-deficient mutant, significantly increased the activity of MLK3 and JNK3 after kainate stimulation. SUMOylation deficiency attenuated the kainate-stimulated interaction between MLK3 and GluK2. In addition, inhibition of kainate-evoked GluK2 endocytosis decreased the activation of MLK3-JNK3 signaling and the binding of MLK3-GluK2 in cultured cortical neurons. These results suggest that the internalization of GluK2 following SUMO modification promotes its binding with MLK3, thereby activating the MLK3-JNK3 pathway, which may be responsible for ischemic neuronal cell death.

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