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Regulation of the Oligomeric Status of CCR3 with Binding Ligands Revealed by Single-Molecule Fluorescence Imaging
Biochemistry ( IF 2.9 ) Pub Date : 2017-10-30 00:00:00 , DOI: 10.1021/acs.biochem.7b00676
Yanzhuo Song 1 , Baosheng Ge 1 , Jun Lao 1 , Zhencai Wang 1 , Bin Yang 1 , Xiaojuan Wang 1 , Hua He 1 , Jiqiang Li 1 , Fang Huang 1
Affiliation  

The relationship between the oligomeric status and functions of chemokine receptor CCR3 is still controversial. We use total internal reflection fluorescence microscopy at the single-molecule level to visualize the oligomeric status of CCR3 and its regulation of the membrane of stably transfected T-REx-293 cells. We find that the population of the dimers and oligomers of CCR3 can be modulated by the binding of ligands. Natural agonists can induce an increase in the level of dimers and oligomers at high concentrations, whereas antagonists do not have a significant influence on the oligomeric status. Moreover, monomeric CCR3 exhibits a stronger chemotactic response in the migration assay of stably transfected CCR3 cells. Together, these data support the notion that CCR3 exists as a mixture of monomers and dimers under nearly physiological conditions and the monomeric CCR3 receptor is the minimal functional unit in cellular signaling transduction. To the best of our knowledge, these results constitute the first report of the oligomeric status of CCR3 and its regulation.

中文翻译:

CCR3的寡聚状态与结合配体的单分子荧光成像揭示的调控。

趋化因子受体CCR3的寡聚状态与功能之间的关系仍存在争议。我们在单分子水平上使用全内反射荧光显微镜观察CCR3的寡聚状态及其对稳定转染的T-REx-293细胞膜的调节。我们发现,CCR3的二聚体和寡聚体可以通过配体的结合进行调节。天然激动剂可以诱导高浓度下的二聚体和寡聚体水平增加,而拮抗剂对寡聚体状态没有显着影响。而且,在稳定转染的CCR3细胞的迁移测定中,单体CCR3表现出更强的趋化反应。一起,这些数据支持以下观点:CCR3在几乎生理条件下以单体和二聚体的混合物形式存在,而单体CCR3受体是细胞信号转导中的最小功能单元。据我们所知,这些结果构成了CCR3寡聚状态及其调控的首次报道。
更新日期:2017-10-31
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