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.
Biochem Biophys Res Commun. 2020 Sep 10;:
Authors: Chen X, Dang X, Song J, Wang G, Liu C, Cui L, Huang Z
Abstract
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.
PMID: 32921411 [PubMed - as supplied by publisher]

Source: Biochemical and Biophysical Research communications - September 9, 2020 Category: Biochemistry Authors: Chen X, Dang X, Song J, Wang G, Liu C, Cui L, Huang Z Tags: Biochem Biophys Res Commun Source Type: research