TRPM4 and PLCβ3 contribute to normal behavioral responses to an array of sweeteners and carbohydrates but PLCβ3 is not needed for taste-driven licking for glucose
TRPM4 and PLCβ3 contribute to normal behavioral responses to an array of sweeteners and carbohydrates but PLCβ3 is not needed for taste-driven licking for glucose
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DOI：
10.1093/chemse/bjae001
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发表时间：
2024-01-01
期刊：
影响因子：
3.5
通讯作者：
Torregrossa，Ann-Marie
中科院分区：
文献类型：
--
作者：
Ascencio Gutierrez，Verenice;Martin，Laura E.;Torregrossa，Ann-Marie
外围味觉系统比以前认为的要复杂得多。新的味觉信号蛋白TRPM4和PLCβ3似乎在正常味觉反应中发挥作用，作为II型味觉细胞信号传导的一部分，或作为广义反应（BR）味觉细胞的一部分，可以对某些或所有种类的味觉物质做出反应。这项工作开始解开II型味觉细胞（TRPM5、TRPM4和IP3R3）或BR味觉细胞（PLCβ3和TRPM4）中发现的细胞内成分在短时味觉测试中驱动对各种糖和其他甜味剂的行为反应中的作用。我们发现，与野生型相比，TRPM4、TRPM5、TRPM4/5和IP3R3敲除（KO）小鼠对所有刺激的反应都表现出迟钝或消失。然而，IP3R3 KO小鼠在对两种糖进行了广泛的接触后，对葡萄糖的舔舐多于对果糖的舔舐。plc - β3 KO小鼠除了对葡萄糖表现出正常的浓度依赖性反应外，对所有刺激均无反应。结果表明，除了葡萄糖外，与II型和BR味觉细胞相关的关键细胞内信号蛋白在味觉驱动反应中是相互需要的。这证实并扩展了先前的发现，即II型和BR细胞都是味觉驱动的舔糖所必需的。葡萄糖似乎参与独特的细胞内味觉信号传导机制，这仍有待充分阐明。
The peripheral taste system is more complex than previously thought. The novel taste-signaling proteins TRPM4 and PLCβ3 appear to function in normal taste responding as part of Type II taste cell signaling or as part of a broadly responsive (BR) taste cell that can respond to some or all classes of tastants. This work begins to disentangle the roles of intracellular components found in Type II taste cells (TRPM5, TRPM4, and IP3R3) or the BR taste cells (PLCβ3 and TRPM4) in driving behavioral responses to various saccharides and other sweeteners in brief-access taste tests. We found that TRPM4, TRPM5, TRPM4/5, and IP3R3 knockout (KO) mice show blunted or abolished responding to all stimuli compared with wild-type. IP3R3 KO mice did, however, lick more for glucose than fructose following extensive experience with the 2 sugars. PLCβ3 KO mice were largely unresponsive to all stimuli except they showed normal concentration-dependent responding to glucose. The results show that key intracellular signaling proteins associated with Type II and BR taste cells are mutually required for taste-driven responses to a wide range of sweet and carbohydrate stimuli, except glucose. This confirms and extends a previous finding demonstrating that Type II and BR cells are both necessary for taste-driven licking to sucrose. Glucose appears to engage unique intracellular taste-signaling mechanisms, which remain to be fully elucidated.