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

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.

• Authors: Yan Liu, Xin Tian, Pingyang Ke, Juan Gu, Yuanlin Ma, Yi Guo, Xin Xu, Yuanyuan Chen, Min Yang, Xuefeng Wang, Fei Xiao
• Journal: Neuroscience bulletin (Neurosci Bull) Vol. 38 Issue 8 Pg. 841-856 (Aug 2022) ISSN: 1995-8218 [Electronic] Singapore
• PMID: 35678994 (Publication Type: Journal Article)
• Copyright: © 2022. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences Supplementary material is available in the online version of this article at http://dx.doi.org/.

Chemical References

• KIF17 protein, mouse
• NR2B NMDA receptor
• Receptors, N-Methyl-D-Aspartate
• Kinesins

Topics

• Animals
• Epilepsy (chemically induced, genetics, metabolism)
• Kinesins (genetics, metabolism)
• Mice
• Neurons (metabolism)
• Receptors, N-Methyl-D-Aspartate (genetics, metabolism)
• Seizures (chemically induced, genetics, metabolism)