The Chemokine CCL2 Promotes Excitatory Synaptic Transmission in Hippocampal Neurons via GluA1 Subunit Trafficking.
10.1007/s12264-024-01236-9
- Author:
En JI
1
;
Yuanyuan ZHANG
2
;
Zhiqiang LI
2
;
Lai WEI
2
;
Zhaofa WU
2
;
Yulong LI
2
;
Xiang YU
3
;
Tian-Jia SONG
4
,
5
Author Information
1. Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.
2. State Key Laboratory of Membrane Biology, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, and IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
3. State Key Laboratory of Membrane Biology, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, and IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China. yuxiang01@pku.edu.cn.
4. State Key Laboratory of Membrane Biology, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, and IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China. ssystj0730@
5. com.
- Publication Type:Journal Article
- Keywords:
AMPA receptor;
CCL2;
CCR2;
CaMKII;
GluA1;
MCP-1;
Synaptic transmission
- MeSH:
Animals;
Receptors, AMPA/metabolism*;
Chemokine CCL2/metabolism*;
Hippocampus/drug effects*;
Neurons/drug effects*;
Synaptic Transmission/drug effects*;
Mice;
Receptors, CCR2/metabolism*;
Protein Transport/drug effects*;
Mice, Inbred C57BL;
Cells, Cultured;
Mice, Knockout;
Excitatory Postsynaptic Potentials/drug effects*;
Rats
- From:
Neuroscience Bulletin
2024;40(11):1649-1666
- CountryChina
- Language:English
-
Abstract:
The CC chemokine ligand 2 (CCL2, also known as MCP-1) and its cognate receptor CCR2 have well-characterized roles in chemotaxis. CCL2 has been previously shown to promote excitatory synaptic transmission and neuronal excitability. However, the detailed molecular mechanism underlying this process remains largely unclear. In cultured hippocampal neurons, CCL2 application rapidly upregulated surface expression of GluA1, in a CCR2-dependent manner, assayed using SEP-GluA1 live imaging, surface GluA1 antibody staining, and electrophysiology. Using pharmacology and reporter assays, we further showed that CCL2 upregulated surface GluA1 expression primarily via Gαq- and CaMKII-dependent signaling. Consistently, using i.p. injection of lipopolysaccharide to induce neuroinflammation, we found upregulated phosphorylation of S831 and S845 sites on AMPA receptor subunit GluA1 in the hippocampus, an effect blocked in Ccr2-/- mice. Together, these results provide a mechanism through which CCL2, and other secreted molecules that signal through G-protein coupled receptors, can directly regulate synaptic transmission.
