Kainate receptors GluK1 and GluK2 differentially regulate synapse morphology

Gui-Fang Duan; Xiao-Hui Tang; Min Jia; Dan Wu; Yun Stone Shi

doi:10.1002/syn.22255

Kainate receptors GluK1 and GluK2 differentially regulate synapse morphology

Synapse. 2023 Jan;77(1):e22255. doi: 10.1002/syn.22255. Epub 2022 Sep 26.

Authors

Gui-Fang Duan¹, Xiao-Hui Tang², Min Jia³, Dan Wu⁴, Yun Stone Shi⁴

Affiliations

¹ State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
² Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
³ Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
⁴ Minister of Education Key Laboratory of Model Animal for Disease Study, Department of Neurology, Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.

PMID: 36121930
DOI: 10.1002/syn.22255

Abstract

The regulation of dendritic spine morphology is a critical aspect of neuronal network refinement during development and modulation of neurotransmission. Previous studies revealed that glutamatergic transmission plays a central role in synapse development. AMPA receptors and NMDA receptors regulate spine morphology in an activity dependent manner. However, whether and how Kainate receptors (KARs) regulate synapse development remains poorly understood. In this study, we found that GluK1 and GluK2 may play distinct roles in synapse development. In primary cultured hippocampal neurons, we found overexpression of the calcium-permeable GluK2(Q) receptor variant increased spine length and spine head area compared to overexpression of the calcium-impermeable GluK2(R) variant or EGFP transfected, control neurons, indicating that Q/R editing may play a role in GluK2 regulation of synapse development. Intriguingly, neurons transfected with GluK1(Q) showed decreased spine length and spine head area, while the density of dendritic spines was increased, suggesting that GluK1(Q) and GluK2(Q) have different effects on synaptic development. Swapping the critical domains between GluK2 and GluK1 demonstrated the N-terminal domain (NTD) is responsible for the different effects of GluK1 and GluK2. In conclusion, Kainate receptors GluK1 and GluK2 have distinct roles in regulating spine morphology and development, a process likely relying on the NTD.

Keywords: Kainate receptors; glutamate receptors; hippocampal neurons; synapse.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Calcium*
Receptors, AMPA
Receptors, Kainic Acid* / genetics
Receptors, N-Methyl-D-Aspartate
Synapses

Substances

Receptors, Kainic Acid
Calcium
Receptors, AMPA
Receptors, N-Methyl-D-Aspartate