Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, College Station, TX 77845, USA.
Cell. 2012 Nov 21;151(5):1113-25. doi: 10.1016/j.cell.2012.10.024.
Internal nutrient sensors play important roles in feeding behavior, yet their molecular structure and mechanism of action are poorly understood. Using Ca(2+) imaging and behavioral assays, we show that the gustatory receptor 43a (Gr43a) functions as a narrowly tuned fructose receptor in taste neurons. Remarkably, Gr43a also functions as a fructose receptor in the brain. Interestingly, hemolymph fructose levels are tightly linked to feeding status: after nutritious carbohydrate consumption, fructose levels rise several fold and reach a concentration sufficient to activate Gr43a in the brain. By using different feeding paradigms and artificial activation of Gr43a-expressing brain neurons, we show that Gr43a is both necessary and sufficient to sense hemolymph fructose and promote feeding in hungry flies but suppress feeding in satiated flies. Thus, our studies indicate that the Gr43a-expressing brain neurons function as a nutrient sensor for hemolymph fructose and assign opposing valence to feeding experiences in a satiation-dependent manner.
内部营养传感器在进食行为中发挥着重要作用,但它们的分子结构和作用机制还了解甚少。我们使用 Ca(2+)成像和行为分析方法表明,味觉受体 43a (Gr43a) 在味觉神经元中作为一种窄谱果糖受体发挥作用。值得注意的是,Gr43a 也在大脑中作为果糖受体发挥作用。有趣的是,血液中的果糖水平与进食状态密切相关:在摄入营养丰富的碳水化合物后,果糖水平会升高数倍,并达到足以激活大脑中 Gr43a 的浓度。通过使用不同的进食模式和人工激活表达 Gr43a 的大脑神经元,我们表明 Gr43a 既是感知血液中果糖和促进饥饿果蝇进食所必需的,也是抑制饱食果蝇进食所必需的。因此,我们的研究表明,表达 Gr43a 的大脑神经元作为血液中果糖的营养传感器,并以饱腹感依赖的方式赋予进食体验相反的效价。