Mechanisms for regulation of glycosylphosphatidylinositol biosynthesis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02415
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Osaka University
• Principal Investigator: Kinoshita Taroh 大阪大学, 微生物病研究所, 特任教授(常勤) (10153165)
• Co-Investigator(Kenkyū-buntansha): 村上 良子 大阪大学, 微生物病研究所, 特任教授 (00304048)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: GPIアンカー / グリコシルホスファチジルイノシトール

Outline of Final Research Achievements

This research project aimed to achieve three goals: 1) Understanding how GPI biosynthesis is upregulated; 2) Characterization of protein(s) involved in translocation of the second GPI biosynthetic intermediate from the cytoplasmic side to the luminal side of the endoplasmic reticulum membrane; 3) Characterization of un-linked free GPIs and intracellular trafficking of free GPI and GPI intermediates. For goal 1, we found accumulated precursors of specific GPI-anchored proteins, such as CD55 and CD48, upregulate GPI biosynthesis together with ARV1. For goal 2, we identified CLPTM1L as a lipid scramblase that is involved in transmembrane translocation of the second GPI intermediate, glucosamine-phosphatidylinositol. For goal 3, we characterized intracellular trafficking of free GPIs and various GPI biosynthetic intermediates.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

GPIの生合成は形態形成、生体防御、神経系形成、受精などに必須であり、GPI生合成の欠損は先天性グリコシルホスファチジルイノシトール(GPI)欠損症や発作性夜間ヘモグロビン尿症といった重篤な疾患を引き起こす。GPI生合成に関する徹底した研究は、生体の生理と病理の理解に重要である。本研究により得られた、GPI生合成量の制御機構に関する成果やGPI生合成中間体とフリーGPIの細胞内動態に関する成果は、GPI生合成とGPI欠損症に関わる知見を一層深化させることにより生体の生理と病理の理解に資する。