Studies on the functions and intracellular transport mechanisms of lipids involved in the formation of cell membrane structure

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03227
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Kyushu University
• Principal Investigator: Ikenouchi Junichi 九州大学, 理学研究院, 教授 (10500051)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: スフィンゴミエリン / アピカル膜 / 上皮細胞 / 微絨毛 / mTORC2シグナル / Rab35 / 低浸透圧ストレス / 細胞死

Outline of Final Research Achievements

In this research project, I elucidated the molecular mechanism that controls the intracellular transport of sphingomyelin, a lipid involved in the formation of membrane structures of epithelial cells. Lysenin, a protein derived from Eisenia fetida that specifically binds to sphingomyelin, was modified to create a probe for visualizing the process of transport of sphingomyelin to the apical membrane. We performed the inhibitor library screening on cells that stably express this probe. We revealed that the mTORC2 pathway regulates the intracellular transport process of sphingomyelin. Furthermore, we found that the small G protein Rab35 is activated in the downstream of the mTORC2 pathway and regulates the transport of sphingomyelin to the apical membrane.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

mTORC2シグナル伝達経路は、細胞の増殖や細胞の運動に関わるシグナル伝達経路で、最近では、がん細胞の悪性化との関連が示唆されています。本研究によって、mTORC2シグナル伝達経路は、細胞膜脂質のスフィンゴミエリンの輸送を制御するという新たな役割を担っていることが明らかになりました。この発見は、上皮細胞に由来する様々な疾患に対する新たな治療法を開発する上で基礎となる知見です。