摘要
The transduction of taste is a fundamental process that allows animals to discriminate nutritious from noxious substances. Three taste modalities, bitter, sweet, and amino acid, are mediated by G protein-coupled receptors that signal through a common transduction cascade: activation of phospholipase C β2 (PLCβ2), leading to a breakdown of phosphatidyinosito1-4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) which causes release of Ca2+ from intracellular stores. The ion channel, TRPM5, is an essential component of this cascade, however the mechanism by which it is activated is not known.
In this thesis I have studied mouse TRPM5 in heterologous expression system and I describe (1) mechanism of activation of TRPM5 by Ca 2+; (2) the role of PIP, in desensitization of TRPM5; (3) voltage dependence of TRPM5 gating; (4) proton block of TRPM5.
These results will help to characterize the properties of TRPM5 in the native cells.
摘要译文
味觉传导是一个基本的过程，可以让动物区分营养和有毒物质。苦味，甜味和氨基酸三味，是通过G蛋白偶联受体介导的，所述G蛋白偶联受体通过共同的转导级联发出信号：磷脂酶Cβ2（PLCβ2）的激活，导致磷脂酰肌醇1-4的分解，（PIP 2）转化为二酰甘油（DAG）和1,4,5-三磷酸肌醇（IP 3），其引起细胞内储存的Ca 2 S释放。离子通道TRPM5，是这个级联的一个重要组成部分，然而它被激活的机制是未知的。本论文研究了小鼠TRPM5在异源表达系统中的作用，并阐述了（1）CaMV2激活TRPM5的机制; （2）PIP在TRPM5的脱敏中的作用;（3）TRPM5门控的电压依赖性; （4）TRPM5的质子块。这些结果将有助于表征TRPM5在原生细胞中的特性。
Liu, Dan. Activation and regulation of the taste transduction channel TRPM5[D]. US: University of Southern California, 2004