Elucidation of novel mechanisms for apical targeting of transmembrane proteins in epithelial cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15364
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kyushu University
• Principal Investigator: Kohda Akira 九州大学, 医学研究院, 助教 (10814650)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 上皮細胞 / apical膜 / NADPH oxidase / 膜貫通蛋白質 / 極性輸送

Outline of Final Research Achievements

Epithelial cells, covering the luminal surfaces of the most internal organs, play an essential role in various physiological functions, such as transporter function and host defense response against microbial infection. Transmembrane proteins expressed in epithelial cells are specifically localized to epithelial cell-specific plasma membrane domains, apical or basolateral membrane, and thereby contribute to the epithelial physiology. In the present study, we clarified the molecular mechanisms whereby NoxIBAR, a novel regulatory protein that we recently identified, regulates apical targeting of transmembrane protein NADPH oxidases (Nox). Furthermore, we also revealed that in addition to Nox, NoxIBAR is required for the apical localization of other transmembrane proteins, suggesting that apical targeting by NoxIBAR is a common mechanism for apical membrane proteins.

Free Research Field

生化学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究を通じて、国内外の研究において長年未解明なままであった「上皮細胞において一部の膜蛋白質はどうしてapical膜に特異的に局在することができるのか」という疑問に対して、部分的ではあるがその答えを得ることができた。上皮細胞の機能を支える分子基盤の理解に繋がるはずである。また、本研究では液-液相分離がapical膜局在制御に関与することを初めて明らかにすることができ、今後「液-液相分離の視点」からapical膜局在制御の分子機構について更なる理解が得られることが期待された。