Analysis of relationship between neuregulin-cleavage and activity upon myelination by using visualization tecnique

Research Project

Project/Area Number	24790262
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	General pharmacology
Research Institution	Juntendo University
Principal Investigator	KASHIYAMA Taku 順天堂大学, 医学部, 助教 (90338343)
Project Period (FY)	2012-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords	ニューレグリン / ミエリン / ErbB / BACE1 / 神経細胞 / 細胞間シグナル伝達 / シナプス / 抑制性ニューロン / ＢＡＣＥ１
Outline of Final Research Achievements	Intercellular signaling through axonal Neuregulin-1 (NRG1) and ErbB receptor tyrosine kinase in Schwann cell or oligodendrocyte is important for myelination. It is believed that cleavage of NRG1 to present its EGF-like growth factor to ErbB receptor is essential for ErbB activation. It is reported that cleavage of NRG1 by different enzymes result in different effects on myelination. But the molecular mechanism is remain to be elucidated. In this study, we elucidated cleavage mechanism of NRG1 in detail and determined its cleavage sites. We successfully prepared anti-NRG1 cleavage-end specific antibody to detect and visualize its cleavage. We revealed the relationship between NRG1 cleavage and ErbB acitivation by establishing juxtacrine reconstitution system using cultured cells.