IMR Press / JIN / Volume 19 / Issue 3 / DOI: 10.31083/j.jin.2020.03.99
Open Access Original Research
Clathrin-independent but dynamin-dependent mechanisms mediate Ca2+-triggered endocytosis of the glutamate GluK2 receptor upon excitotoxicity
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1 Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Jiangsu, 221004, P. R. China
2 Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Jiangsu, 221004, P. R. China
*Correspondence: zhuqiuju@xzhmu.edu.cn (Qiu-Ju Zhu)
J. Integr. Neurosci. 2020, 19(3), 449–458; https://doi.org/10.31083/j.jin.2020.03.99
Submitted: 9 April 2020 | Revised: 1 September 2020 | Accepted: 14 September 2020 | Published: 30 September 2020
Copyright: © 2020 Du et al. Published by IMR Press.
This is an open access article under the CC BY-NC 4.0 license (https://creativecommons.org/licenses/by-nc/4.0/).
Abstract

We first explore the features of GluK2 endocytosis during kainate excitotoxicity and then explore the role of Ca2+ in the regulation of GluK2 endocytosis. The roles of Ca2+ were examined by treating cells with Ca2+ 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 Ca2+/calcineurin signaling. Protein-interacting with C kinase 1-GluK2 interaction is regulated by Ca2+/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 Ca2+ transient. This work indicates the roles of the Ca2+ network in the regulation of GluK2 endocytosis during kainate excitotoxicity.

Keywords
GluK2 endocytosis
Calcium
calcineurin
excitotoxicity
Figures
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