Liman E R
University of Southern California, 3641 Watt Way, Los Angeles, CA 90089, USA.
Handb Exp Pharmacol. 2007(179):287-98. doi: 10.1007/978-3-540-34891-7_17.
TRPM5 is a cation channel that it is essential for transduction of bitter, sweet and umami tastes. Signaling of these tastes involves the activation of G protein-coupled receptors that stimulate phospholipase C (PLC) beta2, leading to the breakdown of phosphatidylinositol bisphosphate (PIP2) into diacylglycerol (DAG) and inositol trisphosphate (IP3), and release of Ca2+ from intracellular stores. TRPM5 forms a nonselective cation channel that is directly activated by Ca2+ and it is likely to be the downstream target of this signaling cascade. Therefore, study of TRPM5 promises to provide insight into fundamental mechanisms of taste transduction. This review highlights recent work on the mechanisms of activation of the TRPM5 channel. The mouse TRPM5 gene encodes a protein of 1,158 amino acids that is proposed to have six transmembrane domains and to function as a tetramer. TRPM5 is structurally most closely related to the Ca(2+)-activated channel TRPM4 and it is more distantly related to the cold-activated channel TRPM8. In patch clamp recordings, TRPM5 channels are activated by micromolar concentrations of Ca2+ and are permeable to monovalent but not divalent cations. TRPM5 channel activity is strongly regulated by voltage, phosphoinositides and temperature, and is blocked by acid pH. Study of TRPM4 and TRPM8, which show similar modes of regulation, has yielded insights into possible structural domains of TRPM5. Understanding the structural basis for TRPM5 function will ultimately allow the design of pharmaceuticals to enhance or interfere with taste sensations.
瞬时受体电位阳离子通道蛋白5（TRPM5）是一种阳离子通道，对于苦味、甜味和鲜味的转导至关重要。这些味觉的信号传导涉及G蛋白偶联受体的激活，该受体刺激磷脂酶C（PLC）β2，导致磷脂酰肌醇二磷酸（PIP2）分解为二酰基甘油（DAG）和肌醇三磷酸（IP3），并从细胞内储存中释放Ca2+。TRPM5形成一个非选择性阳离子通道，该通道直接由Ca2+激活，并且可能是该信号级联反应的下游靶点。因此，对TRPM5的研究有望为味觉转导的基本机制提供深入了解。本综述重点介绍了TRPM5通道激活机制的最新研究成果。小鼠TRPM5基因编码一种由1158个氨基酸组成的蛋白质，该蛋白质被认为具有六个跨膜结构域，并作为四聚体发挥作用。TRPM5在结构上与Ca(2+)激活通道TRPM4关系最为密切，与冷激活通道TRPM8的关系则较为疏远。在膜片钳记录中，TRPM5通道由微摩尔浓度的Ca2+激活，对单价阳离子而非二价阳离子具有通透性。TRPM5通道活性受到电压、磷酸肌醇和温度的强烈调节，并被酸性pH阻断。对TRPM4和TRPM８的研究显示出相似的调节模式，这为TRPM5可能的结构域提供了见解。了解TRPM5功能的结构基础最终将有助于设计增强或干扰味觉的药物。
