Mechanism of Notch receptor signaling and its dependency on lipids

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06038
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Sato Takeshi 京都薬科大学, 薬学部, 教授 (90403013)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Notchシグナリング / Context dependency

Outline of Final Research Achievements

One of the most scientifically interesting phenomena in Notch signaling is its "context dependency". This context dependency can be explained as follow: Notch ligands activate distinct target through the same receptor. In this project we decided to get insight on the molecular mechanism of this phenomenon.
We have worked on molecular dynamics on looking at Notch ligand and certain lipids and found that each kind of ligand has preference in binding for a certain lipid such as GM1 or GM3. This selectivity, or specificity, may explain the context dependency. "Wet" experiments are in progress to verify the validity of results from the MD simulation.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

Notch受容体に関する基礎研究は発生学分野が中心となり、細胞生物学、生化学的研究が行われるようになった。疾患との関連も深く、医学、創薬的にも関心の高い研究対象であり、多くの研究がなされている。このシグナリングにおけるcontext dependency機構の解明は、受容体と脂質との協奏機構を解き明かす上で重要であり、本研究結果は今後の当該研究分野における道筋を示すものであると考えられる。