S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biomedical Sciences (대학원 의과학과) Theses (Ph.D. / Sc.D._의과학과)
Novel finding for screening Small G proteins influencing transient receptor potential canonical 4 (TRPC4) channels
TRPC4 이온통로에 영향을 미치는 Small G protein의 스크리닝을 통한 새로운 발견
- 의과대학 의과학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의과학과, 2015. 2. 서인석.
- Canonical transient receptor potential 4 (TRPC4) channels are calcium-permeable, non-selective cation channels that are widely distributed in mammalian cells. It is generally speculated that TRPC4 channels are activated by Gq/11-PLC pathway or directly activated by Gi/o proteins. Although many mechanistic studies regarding TRPC4 have dealt with heterotrimeric G-proteins, here, we first report the functional relationship between TRPC4 and small GTPase. We performed patch clamp, western blotting, and FRET technique. Rab proteins, Rasd1, Rasd2, and Rit protein increased without GTPS. Rasd1 selectively activated TRPC4 channels and it was the Ras protein among small G protein families that can potently activate TRPC4 channels. For this to occur, it was found that certain population of functional Gαi1 protein is essential. Meanwhile, dexamethasone, a synthetic gluco-corticoid and anti-inflammatory drug were known to increase mRNA level of Rasd1 in pancreatic β-cells. We have found that dexamethasone triggers TRPC4-like cationic current in INS-1 cells via increasing protein expression level of Rasd1. This relationship among dexamethasone, Rasd1 and TRPC4 could suggest a new therapeutic agent for hospitalized diabetes mellitus (DM) patients with prolonged dexamethasone prescription.