Elucidation of the mechanisms of subcellular localization of the prostaglandin transporter

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22719
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Takasaki University of Health and Welfare
• Principal Investigator: Nakamura Yoshinobu 高崎健康福祉大学, 薬学部, 助教 (60880317)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: SLCO2A1 / プロスタグランジン / N型糖鎖修飾 / 細胞内局在

Outline of Final Research Achievements

Prostaglandin (PG) transporter SLCO2A1 plays an important role in the regulation of PG actions. Its loss of function is responsible for two refractory diseases, pachydermoperiostosis (PDP) and chronic enteropathy associated with SLCO2A1 (CEAS). We found that SLCO2A1 localizes differently at the plasma membrane and/or intracellular vesicles depending on the cell types. This differential localization modulates PG actions in opposite directions, "attenuated" and "enhanced," however the mechanisms of subcellular localization of SLCO2A1 remain unclear. In this study, we found that N-glycosylation, a post-translational modification, is one of the localization regulators that modulates the plasma membrane expression levels of SLCO2A1.

Free Research Field

薬物動態学、薬理学

Academic Significance and Societal Importance of the Research Achievements

PDPとCEASはいずれも有効な治療法がない指定難病である。どちらもSLCO2A1が原因遺伝子として同定されているが、SLCO2A1の機能喪失によって病態が形成される仕組みは十分に解明されていない。本研究成果であるN型糖鎖がSLCO2A1の細胞内局在を調節するという発見は、種々の細胞に幅広く発現するSLCO2A1の生理的役割を理解する上で重要な知見であり、将来的にPDPとCEASの病態解明に繋がる可能性がある。