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

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.
Mesh Terms:
Animals, Brain Ischemia, CA1 Region, Hippocampal, COS Cells, Cell Line, Tumor, Chlorocebus aethiops, Enzyme Activation, Humans, Kainic Acid, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, Male, Mitogen-Activated Protein Kinase 10, Phosphorylation, Protein Transport, Rats, Rats, Sprague-Dawley, Receptors, Kainic Acid, Sumoylation
FEBS Lett
Date: May. 07, 2012
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