Key Laboratory of Marine Drugs, Ministry of Education and Qingdao National Laboratory for Marine Science & Technology and Shandong Provincial Key Lab of Glycoscience & Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
Department of Molecular Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
Angew Chem Int Ed Engl. 2018 Jan 22;57(4):967-971. doi: 10.1002/anie.201706535. Epub 2018 Jan 2.
Glycans anchored on cell-surface receptors are active modulators of receptor signaling. A strategy is presented that enforces transient changes to cell-surface glycosylation patterns to tune receptor signaling. This approach, termed in situ glycan editing, exploits recombinant glycosyltransferases to incorporate monosaccharides with linkage specificity onto receptors in situ. α2,3-linked sialic acid or α1,3-linked fucose added in situ suppresses signaling through epidermal growth factor receptor and fibroblast growth factor receptor. We also applied the same strategy to regulate the electrical signaling of a potassium ion channel-human ether-à-go-go-related gene channel. Compared to gene editing, no long-term perturbations are introduced to the treated cells. In situ glycan editing therefore offers a promising approach for studying the dynamic role of specific glycans in membrane receptor signaling and ion channel functions.
细胞表面受体上锚定的聚糖是受体信号的活性调节剂。本文提出了一种策略，即通过瞬时改变细胞表面糖基化模式来调节受体信号。这种方法称为原位糖基编辑，利用重组糖基转移酶将具有连接特异性的单糖原位掺入受体中。原位添加的α2,3 连接唾液酸或α1,3 连接岩藻糖抑制表皮生长因子受体和成纤维细胞生长因子受体的信号转导。我们还应用相同的策略来调节钾离子通道-人类 ether-à-go-go 相关基因通道的电信号。与基因编辑相比，处理过的细胞不会引入长期干扰。因此，原位糖基编辑为研究特定糖在膜受体信号和离子通道功能中的动态作用提供了一种很有前途的方法。
