Browse

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

Cited 0 time in Web of Science Cited 0 time in Scopus
Authors
위진홍
Advisor
서인석
Major
의과대학 의과학과
Issue Date
2015-02
Publisher
서울대학교 대학원
Keywords
TRPC4Small G proteinRasd1GPCRDexamethasoneInsulin
Description
학위논문 (박사)-- 서울대학교 대학원 : 의과학과, 2015. 2. 서인석.
Abstract
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 GTPS. 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.
Language
English
URI
http://hdl.handle.net/10371/122280
Files in This Item:
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Theses (Ph.D. / Sc.D._의과학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse