Key Laboratory for Advanced Materials & Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology , 130 Meilong Road, Shanghai 200237, P. R. China.
National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 189 Guo Shoujing Road, Shanghai 201203, P. R. China.
ACS Appl Mater Interfaces. 2017 May 3;9(17):14709-14715. doi: 10.1021/acsami.7b02754. Epub 2017 Apr 20.
Agonist-induced activation and endocytosis of G protein-coupled receptors (GPCRs) are crucial for a number of physiological and pathological processes. However, tools that are available for probing GPCR endocytosis have been insufficient. Here, we developed a two-dimensional (2D) material agonist by supramolecular self-assembly between an endogenous agonist of κ-opioid receptor (KOR) and 2D molybdenum disulfide. The 2D material agonist has proven to be amenable for eliciting GPCR activation and endocytosis in cells stably expressing KOR rather than in those without KOR expression. Using super-resolution microscopy, we also show that the 2D material agonist colocalizes well with GFP-fused KOR intracellularly. Further, the endocytosed 2D material agonist can selectively produce reactive oxygen species in cells that overly express KOR, as controlled by light irradiation.
激动剂诱导的 G 蛋白偶联受体 (GPCR) 的激活和内化对于许多生理和病理过程至关重要。然而，可用于探测 GPCR 内化的工具一直不足。在这里，我们通过 κ 阿片受体 (KOR) 的内源性激动剂和二维二硫化钼之间的超分子自组装，开发了一种二维 (2D) 材料激动剂。事实证明，这种 2D 材料激动剂适用于在稳定表达 KOR 的细胞中诱导 GPCR 激活和内化，而不适用于没有 KOR 表达的细胞。使用超分辨率显微镜，我们还表明，2D 材料激动剂与 GFP 融合的 KOR 在细胞内很好地共定位。此外，被内化的 2D 材料激动剂可以在过度表达 KOR 的细胞中选择性地产生活性氧，这可以通过光照射来控制。
