权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The in vivo roles of PKD1L3 and PKD2L1 in sour taste detection

PKD1L3和PKD2L1在酸味检测中的体内作用

基本信息

批准号：
20780089
负责人：
ISHIMARU Yoshiro
金额：
$ 2.75万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2009
项目状态：
已结题

项目摘要

To elucidate the physiological roles of a candidate sour taste receptor, PKD1L3/PKD2L1, we generated gene knockout mice for PKD1L3 and/or PKD2L1. To investigate phenotype of these mice in taste sensation including sour taste, behavioral and electrophysiological analyses were performed. In the behavioral analyses such as two-bottle preference test and brief-access licking test, PKD1L3, PKD2L1, and double KO mice showed normal preference or avoidance behavior similar to the wild-type littermates for all the five basic taste qualities. In contrast, both whole-nerve and single-fiber chorda tympani nerve responses of PKD2L1 KO and double KO mice to sour solutions such as citric acid, HCl, and acetic acid significantly reduced compared with wild-type mice, while PKD1L3 KO mice showed normal responses. In glossopharyngeal nerve recordings, PKD1L3, PKD2L1, and double KO mice showed normal responses compared with wild-type mice. In addition, PKD1L3, PKD2L1, and double KO mice showed responses s … More imilar to wild-type mice upon stimulation with salt,sweet, bitter, and umami (savory) taste compounds. Collectively, these results demonstrate that PKD2L1 functions as a sour taste receptor in vivo and suggest that there are multiple mechanisms underlying sour taste detection such as somatosensation other than via taste buds.We identified the N-terminal extracellular region of human PKD1L3 and the full-length of human PKD2L1. HEK 293T cells expressing human PKD2L1 and chimeric PKD1L3, which consists of the N-terminal extracellular region of human PKD1L3 and the following region of mouse PKD1L3, showed off-response upon stimulation with sour solution such as citric acid. These cells still showed robust response to sour stimuli in the presence of a taste-modifying protein, neoculin, extracted from Curculigo latifolia. These results raise the possibility that neoculin inhibits the region other than the N-terminal extracellular region of human PKD1L3. Alternatively, inhibition event occurs at the level of taste cells or taste neurons, not at the taste receptors. Less

为了阐明候选酸味受体PKD1L3/PKD2L1的生理作用，我们产生了PKD1L3和/或PKD2L1的基因敲除小鼠。为了研究这些小鼠在味觉包括酸味方面的表型，进行了行为和电生理分析。在行为学分析中，PKD1L3、PKD2L1和双基因敲除小鼠对5种基本味觉品质的偏好或回避行为与野生型小鼠相似。相比之下，与野生型小鼠相比，PKD2L1 KO和双KO小鼠对柠檬酸、HCl和乙酸等酸性溶液的全神经和单纤维鼓索神经反应均显著降低，而PKD1L3 KO小鼠显示正常反应。在舌咽神经记录中，PKD1L3、PKD2L1和双KO小鼠与野生型小鼠相比表现出正常反应。此外，PKD1L3、PKD2L1和双基因敲除小鼠在1000 - 100000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000 ...更多信息类似于野生型小鼠在用咸味、甜味、苦味和鲜味（咸味）化合物刺激时的表现。总的来说，这些结果表明，PKD2L1作为一个酸味受体在体内的功能，并建议有多种机制的酸味检测，如躯体感觉以外通过tastebuds.We确定的N-末端细胞外区域的人PKD1L3和全长的人PKD2L1。表达人PKD2L1和嵌合PKD1L3（由人PKD1L3的N-末端胞外区和小鼠PKD1L3的后续区域组成）的HEK 293 T细胞在用酸性溶液（如柠檬酸）刺激时显示出关闭反应。这些细胞仍然表现出强大的酸性刺激的味觉修饰蛋白，neoculin的存在下，提取的大叶草。这些结果提高了新oculin抑制人PKD1L3的N-末端胞外区以外的区域的可能性。或者，抑制事件发生在味觉细胞或味觉神经元的水平，而不是味觉受体。少