北京大学宋天佳等研究人员合作发现，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。相关论文于2024年7月2日在线发表于国际学术期刊《神经科学通报》。

研究人员发现，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，研究人员进一步发现CCL2主要通过Gα_q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，研究人员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，CCL2通过这种机制与其他通过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。

研究人员表示，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。

附：英文原文

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

Author: Ji, En, Zhang, Yuanyuan, Li, Zhiqiang, Wei, Lai, Wu, Zhaofa, Li, Yulong, Yu, Xiang, Song, Tian-Jia

Issue&Volume: 2024-07-02

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.

DOI: 10.1007/s12264-024-01236-9

Source: https://link.springer.com/article/10.1007/s12264-024-01236-9