N-glycosylation modifies prostaglandin E2 uptake by reducing cell surface expression of SLCO2A1.

Yoshinobu Nakamura, Chisato Aizawa, Hinako Kawata, Takeo Nakanishi

Prostaglandins & other lipid mediators 2023 Apr

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SLCO2A1 functions as a prostaglandin (PG) influx transporter to facilitate intracellular oxidation of PGs and its defect causes dysregulation of PG signaling and metabolism. This study aimed to clarify effects of N-glycosylation on functional SLCO2A1 expression. Putative N-glycosylation site(s) (N134, N478, and/or N491) of human SLCO2A1 were mutated to Q and wild-type (WT) and mutant forms were expressed in HEK293 and human epithelial cells. Molecular weight of WT decreased to nearly 55 kDa by PNGase F treatment and was identical to that of triple mutant (TM, i.e., N134Q/N478Q/N491Q). Transport affinity of TM for PGE2 (Km of 392.7 nM) was comparable to that of WT (Km of 328.5 nM); however, immunoassays showed that TM cell surface expression remained at 24% of WT in HEK293 cells, resulting in a reduced cellular PGE2 uptake. These results suggest N-glycosylation modifies cellular PGE2 uptake by decreasing SLCO2A1 localization to the plasma membrane. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Yoshinobu Nakamura, Chisato Aizawa, Hinako Kawata, Takeo Nakanishi. N-glycosylation modifies prostaglandin E2 uptake by reducing cell surface expression of SLCO2A1. Prostaglandins & other lipid mediators. 2023 Apr;165:106714