We first explore the features of GluK2 endocytosis during kainate excitotoxicity and then explore the role of Ca in the regulation of GluK2 endocytosis. The roles of Ca were examined by treating cells with Ca inhibitors or chelators. Surface biotinylation was used to examine the surface localization of GluK2. Immunoprecipitation followed by immunoblotting was used to identify the interaction of GluK2 with the endocytosis regulator protein-interacting with C kinase 1 and dynamin. Dynamin phosphorylation was examined by immunoblotting with the corresponding antibodies. Our results show that GluK2 internalization is blocked by inhibitors of clathrin-independent endocytosis and relies on intracellular Ca/calcineurin signaling. Protein-interacting with C kinase 1-GluK2 interaction is regulated by Ca/calcineurin signaling. Dynamin participates in the regulation of GluK2 surface localization. Also, calcineurin activation is related to dynamin function during kainate excitotoxicity. In conclusion, GluK2 receptor endocytosis is probably a clathrin-independent and dynamin-dependent process regulated by the peak Ca transient. This work indicates the roles of the Ca network in the regulation of GluK2 endocytosis during kainate excitotoxicity.
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