Research on a possible novel transcriptional regulation by a membrane protein

Research Project

Project/Area Number	16K08066
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Integrative animal science
Research Institution	Hokkaido University
Principal Investigator	Yamaguchi Soichiro 北海道大学, 獣医学研究院, 准教授 (50596864)
Project Period (FY)	2016-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords	TMC1 / 転写調節 / 核内移行 / タンパク質切断 / タンパク質分解 / 膜タンパク質 / 生理学
Outline of Final Research Achievements	Transmembrane channel like protein 1 (TMC1) is the mechanoelectrical transduction (MET) channel in hair cells of the inner ear. I found a phenomenon that the cytosolic N-terminal region of overexpressed mouse TMC1 (mTMC1) is localized in nuclei of a small population of HEK293 cells. This suggests that in some cells the N-terminal region of mTMC1 is cleaved and transported into nuclei. In this study, I revealed the positions of the cleavage of overexpressed mTMC1 and the involvement of Importin α in the mechanism of accumulation of the N-terminal region into nuclei. Moreover, overexpression of the N-terminal fragment of mTMC1 changed the expression levels of several genes. These findings suggest the possibility that TMC1 is cleaved and the produced N-terminal fragment regulates transcription in hair cells of the inner ear. However, further investigation is required in order to prove that the transcriptional regulation by mTMC1 happens in vivo.
Academic Significance and Societal Importance of the Research Achievements	本研究成果は、TMC1という膜タンパク質がその切断を介して転写調節を行う可能性があることを示しており、TMC1の内耳有毛細胞での新しい働きの可能性を提示するものである。すなわち、内耳有毛細胞が例えば障害を受けた時など、TMC1の切断減少が起きた時、その遊離したN端領域が核内に移行して、転写調節を行い、有毛細胞機能を変化させる可能性がある。よって、難聴の病態発現の一つの在り方の解明につながる可能性がある成果となる。