趋化因子 CCL2 通过 GluA1 亚基运输促进海马神经元的兴奋性突触传递

IF 5.9 2区 医学 Q1 NEUROSCIENCES
Neuroscience bulletin Pub Date : 2024-11-01 Epub Date: 2024-07-02 DOI:10.1007/s12264-024-01236-9
En Ji, Yuanyuan Zhang, Zhiqiang Li, Lai Wei, Zhaofa Wu, Yulong Li, Xiang Yu, Tian-Jia Song
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引用次数: 0

摘要

CC 趋化因子配体 2(CCL2,又称 MCP-1)及其同源受体 CCR2 在趋化中的作用已得到充分描述。此前已有研究表明,CCL2 可促进兴奋性突触传递和神经元兴奋性。然而,这一过程的详细分子机制在很大程度上仍不清楚。在培养的海马神经元中,CCL2的应用以CCR2依赖的方式迅速上调了GluA1的表面表达,并使用SEP-GluA1活体成像、表面GluA1抗体染色和电生理学进行了检测。通过药理学和报告实验,我们进一步发现 CCL2 主要通过 Gαq 和 CaMKII 依赖性信号传导来上调表面 GluA1 的表达。与此相一致的是,我们利用注射脂多糖诱导神经炎症,发现海马中 AMPA 受体亚基 GluA1 上 S831 和 S845 位点的磷酸化上调,这种效应在 Ccr2-/-小鼠中被阻断。总之,这些结果提供了一种机制,通过这种机制,CCL2 和其他通过 G 蛋白偶联受体发出信号的分泌分子可以直接调节突触传递。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The Chemokine CCL2 Promotes Excitatory Synaptic Transmission in Hippocampal Neurons via GluA1 Subunit Trafficking.

The Chemokine CCL2 Promotes Excitatory Synaptic Transmission in Hippocampal Neurons via GluA1 Subunit Trafficking.

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.

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来源期刊
Neuroscience bulletin
Neuroscience bulletin NEUROSCIENCES-
CiteScore
7.20
自引率
16.10%
发文量
163
审稿时长
6-12 weeks
期刊介绍: Neuroscience Bulletin (NB), the official journal of the Chinese Neuroscience Society, is published monthly by Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Springer. NB aims to publish research advances in the field of neuroscience and promote exchange of scientific ideas within the community. The journal publishes original papers on various topics in neuroscience and focuses on potential disease implications on the nervous system. NB welcomes research contributions on molecular, cellular, or developmental neuroscience using multidisciplinary approaches and functional strategies. We feature full-length original articles, reviews, methods, letters to the editor, insights, and research highlights. As the official journal of the Chinese Neuroscience Society, which currently has more than 12,000 members in China, NB is devoted to facilitating communications between Chinese neuroscientists and their international colleagues. The journal is recognized as the most influential publication in neuroscience research in China.
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