Evaluation of circadian scaffold protein for diurnal localization of membrane transporter

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23832
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: Tokyo University of Science, Yamaguchi
• Principal Investigator: Tsurudome Yuya 山陽小野田市立山口東京理科大学, 薬学部, 助教 (80846254)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 時間生物学 / 薬物動態学 / 細胞生物学

Outline of Final Research Achievements

For some of the membrane proteins expressed in cells, "scaffold protein" that supports the membrane localization of the membrane protein is indispensable. Na+/H+ exchanger regulatory factor-1 (NHERF1), functions as a scaffold protein, which is implicated in the regulation of circadian membrane expression of various cell-surface proteins.
We found that the diurnal expression of NHERF1 is regulated by the clock gene. In some clock gene disruption model mice, the circadian expression of NHERF1 was abolished by clock gene mutation, and the expression rhythm of the membrane protein which controlled by NHERF1 are altered . In this study, we suggest that changes in the expression rhythm of scaffold proteins are associated with the risk of developing metabolic diseases.

Free Research Field

時間生物学

Academic Significance and Societal Importance of the Research Achievements

機能性分子の発現リズムは時計遺伝子を主体とする転写・翻訳過程か、ユビキチン化によるタンパク質の分解過程に着目して生体機能。しかしながら申請者の研究は、機能性分子の局在過程に着目することで、足場タンパク質の発現リズムによる膜タンパク質の発現リズム制御機構という新たな概念を提示するものである。この制御機構のより詳細な解析を行うことで、膜タンパク質を介した生理機能の概日リズムのより深い解明につながるほか、生体リズム変容によって生じる膜タンパク質の発現変化やその生理機能への影響を明らかとし、膜タンパク質の発現変容を介した代謝性疾患の新たな発症機序解明につながる研究となる。