Molecular mechanisms of lipoquality recognition and identification of functional membrane nanodomain

2021 Fiscal Year Final Research Report

• Project Area: Quality of lipids in biological systems
• Project/Area Number: 15H05901
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: Okamura Yasushi 大阪大学, 医学系研究科, 教授 (80201987)
• Co-Investigator(Kenkyū-buntansha): 中川 敦史 大阪大学, 蛋白質研究所, 教授 (20188890)
• Project Period (FY): 2015-06-29 – 2020-03-31
• Keywords: 脂質 / 蛋白質 / シグナル伝達 / 酵素 / 生理学

Outline of Final Research Achievements

Membrane proteins play important roles in signal transduction in many biological events including brain, heart and endocrine system as well as organ development and growth. Such functions depend on intimate interplay between membrane proteins and lipid molecules. Previously, detailed molecular mechanisms how membrane proteins recognize fine biochemical nature of lipid molecules remained unclear. In this research, we studied molecular mechanisms underlying how membrane proteins, mainly ion channels and voltage sensing proteins, recognize detailed chemical nature (which we call lipoquality) of lipid molecules through combination of electrophysiology, mass spectrometry, structure biology, electron microscopic analysis and fluorometry. We found that voltage sensing phosphatase has key region sensing phospholipid in the membrane interface and that sperm has uneven distribution of phosphoinositides playing important role in sperm function.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかにした分子メカニズムは、精子や免疫細胞に発現する膜タンパク質機能の本質的理解に重要であり、将来的に不妊症や炎症性疾患や認知症の解決につながる基礎を提供するものである。また今後、広く共通する仕組みが見出されることにより、がんや成人病の解決にも寄与できると考えられる。