N-glycosylation of Siglec-15 decreases its lysosome-dependent degradation and promotes its transportation to the cell membrane
N-glycosylation of Siglec-15 decreases its lysosome-dependent degradation and promotes its transportation to the cell membrane
复制标题
Siglec-15 的 N-糖基化减少了其溶酶体依赖性降解并促进其转运至细胞膜
DOI：
10.1016/j.bbrc.2020.08.111
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发表时间：
2020-11-26
影响因子：
3.1
通讯作者：
Huang, Zhenyu
中科院分区：
文献类型：
--
作者：
Chen, Xiaojian;Dang, Xuening;Huang, Zhenyu
最近报道Siglec-15是一种免疫抑制分子，其由肿瘤相关巨噬细胞表达并在一些实体瘤中上调。靶向Siglec-15是正常化癌症免疫治疗的潜在策略。在这里，我们确定了重要的翻译后修饰，Siglec-15的N-糖基化，其受葡萄糖摄取的调节。使用一系列糖苷酶和糖基化抑制剂，我们证明了Siglec-15在体外和体内完全N-糖基化。确定了精确的糖基化位点。N-糖基化通过减少其溶酶体依赖性降解来稳定Siglec-15。通过免疫荧光检测Siglec-15的亚细胞分布表明，N-糖基化促进Siglec-15转运到细胞膜。集体观察表明，靶向Siglec-15的N-糖基化可能是免疫疗法的有效补充。(C)2020年，任作家。爱思唯尔公司出版
Siglec-15 was recently reported to be an immunosuppressive molecule that is expressed by tumor-associated macrophages and upregulated in some solid tumors. Targeting Siglec-15 is a potential strategy for normalization cancer immunotherapy. Here, we identified the important post-translational modification, N-glycosylation of Siglec-15, which is regulated by glucose uptake. Using a series of glycosidase and glycosylation inhibitors, we demonstrated that Siglec-15 was completely N-glycosylated in vitro and in vivo. The precise glycosylation site was determined. N-glycosylation stabilized Siglec-15 by decreasing its lysosome-dependent degradation. Siglec-15 subcellular distribution detected by immunofluorescence indicated that N-glycosylation promoted Siglec-15 transportation to the cell membrane. The collective observations indicate that targeting the N-glycosylation of Siglec-15 may be an effective supplement to immunotherapy. (C) 2020 The Authors. Published by Elsevier Inc.