Bioengineering Interdepartmental Graduate Program, Interdepartmental Neuroscience Program, and Department of Entomology, Institute of Integrative Genome Biology, University of California, Riverside, CA 92521.
Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1598-603. doi: 10.1073/pnas.1311724111. Epub 2014 Jan 13.
Sweet taste cells play critical roles in food selection and feeding behaviors. Drosophila sweet neurons express eight gustatory receptors (Grs) belonging to a highly conserved clade in insects. Despite ongoing efforts, little is known about the fundamental principles that underlie how sweet tastants are detected by these receptors. Here, we provide a systematic functional analysis of Drosophila sweet receptors using the ab1C CO2-sensing olfactory neuron as a unique in vivo decoder. We find that each of the eight receptors of this group confers sensitivity to one or more sweet tastants, indicating direct roles in ligand recognition for all sweet receptors. Receptor response profiles are validated by analysis of taste responses in corresponding Gr mutants. The response matrix shows extensive overlap in Gr-ligand interactions and loosely separates sweet receptors into two groups matching their relationships by sequence. We then show that expression of a bitter taste receptor confers sensitivity to selected aversive tastants that match the responses of the neuron that the Gr is derived from. Finally, we characterize an internal fructose-sensing receptor, Gr43a, and its ortholog in the malaria mosquito, AgGr25, in the ab1C expression system. We find that both receptors show robust responses to fructose along with a number of other sweet tastants. Our results provide a molecular basis for tastant detection by the entire repertoire of sweet taste receptors in the fly and lay the foundation for studying Grs in mosquitoes and other insects that transmit deadly diseases.
甜味细胞在食物选择和进食行为中起着关键作用。果蝇的甜味神经元表达属于昆虫高度保守分支的 8 种味觉受体 (Grs)。尽管人们一直在努力,但对于这些受体如何检测甜味剂的基本原理知之甚少。在这里,我们使用 ab1C CO2 感应嗅觉神经元作为独特的体内解码器,对果蝇甜味受体进行了系统的功能分析。我们发现该组的 8 个受体中的每一个都对一种或多种甜味剂敏感,这表明它们在配体识别中直接发挥作用。受体的反应谱通过对相应 Gr 突变体的味觉反应分析进行验证。反应矩阵显示 Gr-配体相互作用广泛重叠,并根据序列将甜味受体松散地分为两组。然后,我们表明表达苦味受体可使某些令人不快的味觉剂敏感,这些味觉剂与 Gr 衍生的神经元的反应相匹配。最后,我们在 ab1C 表达系统中表征了内部果糖感应受体 Gr43a 及其在疟蚊中的同源物 AgGr25。我们发现这两种受体对果糖以及其他一些甜味剂都有强烈的反应。我们的研究结果为果蝇中整个甜味受体对味觉剂的检测提供了分子基础,并为研究蚊子和其他传播致命疾病的昆虫中的 Grs 奠定了基础。