State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao, 266580, P. R. China.
Sci Rep. 2017 Dec 4;7(1):16873. doi: 10.1038/s41598-017-16802-7.
Dimerization and oligomerization of G-protein coupled receptors (GPCRs) have emerged as important characters during their trans-membrane signal transduction. However, until now the relationship between GPCR dimerization and their trans-membrane signal transduction function is still uncovered. Here, using pertussis toxin (PTX) to decouple the receptor from G protein complex and with single-molecule imaging, we show that in the presence of agonist, cells treated with PTX showed a decrease in the number of dimers and oligomers on the cell surface compared with untreated ones, which suggests that oligomeric status of CXCR4 could be significantly influenced by the decoupling of G protein complex during its signal transduction process. Moreover, with chlorpromazine (CPZ) to inhibit internalization of CXCR4, it was found that after SDF-1α stimulation, cells treated with CPZ showed more dimers and oligomers on the cell surface than untreated ones, which suggest that dimers and oligomers of CXCR4 tend to internalize more easily than monomers. Taken together, our results demonstrate that dimerization and oligomerization of CXCR4 is closely related with its G protein mediated pathway and β-arrestin mediated internalization process, and would play an important role in regulating its signal transduction functions.
G 蛋白偶联受体（GPCRs）的二聚化和寡聚化已成为其跨膜信号转导过程中的重要特征。然而，到目前为止，GPCR 二聚化与其跨膜信号转导功能之间的关系仍未被揭示。在这里，我们使用百日咳毒素（PTX）将受体与 G 蛋白复合物解偶联，并通过单分子成像，显示在激动剂存在的情况下，与未处理的细胞相比，用 PTX 处理的细胞表面的二聚体和寡聚体数量减少，这表明在信号转导过程中，G 蛋白复合物的解偶联可能会显著影响 CXCR4 的寡聚状态。此外，用氯丙嗪（CPZ）抑制 CXCR4 的内化，我们发现在用 SDF-1α 刺激后，用 CPZ 处理的细胞表面的二聚体和寡聚体比未处理的细胞多，这表明 CXCR4 的二聚体和寡聚体比单体更容易内化。总之，我们的结果表明，CXCR4 的二聚化和寡聚化与其 G 蛋白介导的途径和β-arrestin 介导的内化过程密切相关，并在调节其信号转导功能方面发挥重要作用。
