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KIF17 Modulates Epileptic Seizures and Membrane Expression of the NMDA Receptor Subunit NR2B

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Abstract

Epilepsy is a common and severe brain disease affecting >65 million people worldwide. Recent studies have shown that kinesin superfamily motor protein 17 (KIF17) is expressed in neurons and is involved in regulating the dendrite-targeted transport of N-methyl-D-aspartate receptor subtype 2B (NR2B). However, the effect of KIF17 on epileptic seizures remains to be explored. We found that KIF17 was mainly expressed in neurons and that its expression was increased in epileptic brain tissue. In the kainic acid (KA)-induced epilepsy mouse model, KIF17 overexpression increased the severity of epileptic activity, whereas KIF17 knockdown had the opposite effect. In electrophysiological tests, KIF17 regulated excitatory synaptic transmission, potentially due to KIF17-mediated NR2B membrane expression. In addition, this report provides the first demonstration that KIF17 is modified by SUMOylation (SUMO, small ubiquitin-like modifier), which plays a vital role in the stabilization and maintenance of KIF17 in epilepsy.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81873788, 81922023, 82001378, and 82171440), the Chongqing Natural Science Foundation Project (cstc2019jcyj-msxmX0184), and the Fifth Senior Medical Talents Program of Chongqing for Young and Middle-aged.

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Liu, Y., Tian, X., Ke, P. et al. KIF17 Modulates Epileptic Seizures and Membrane Expression of the NMDA Receptor Subunit NR2B. Neurosci. Bull. 38, 841–856 (2022). https://doi.org/10.1007/s12264-022-00888-9

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