The molecular basis of fatty acid taste in Aedes aegypti

摘要 蚊子叮咬不仅仅是一种令人发痒的烦恼--通过蚊子叮咬传播的疾病是主要的 每年的发病和死亡原因，并给医疗保健系统带来沉重的经济负担 环游世界。当昆虫疾病媒介降落在宿主上时，它使用接触式化学传感或味觉来 告知它咬人的决定，从而传播疾病。驱虫剂，其功能是扰乱 包括DEET在内的味觉提示已被证明是有效的拒食剂，但也有明显的局限性。 许多叮咬昆虫，包括登革热媒介埃及伊蚊，叮咬和 与DEET相比，当摄入脂肪酸(FAs)(饮食脂肪中令人愉悦的成分)时，摄取血液的能力更强。 尽管有这样的发现，蚊子的味道，包括FA的味道，使用的受体机制是 很大程度上是未知的，仍未被探索。对果蝇的许多味觉模式进行了广泛的研究 ，它是Ae.的一个双翅目近亲。埃及伊蚊，但对FA味道的分子要求是 悬而未决。为此，我们建议将我们最新的发现应用于强大的模式生物 以确定目前未知的细胞和受体机制的FA味道在Ae。 埃及伊蚊。在果蝇中，低浓度的FAs是吸引人的，而高浓度的FAs是令人厌恶的。在……里面 除了最近的证据表明，味觉对低浓度FAs的吸引力是由特定的 我们实验室的数据表明，味觉感受器神经元(GRN)的亚群和需要磷脂酶C 对G蛋白偶联受体(GPCR)和色氨酸通道的要求。除了它在吸引力方面的作用外， 厌恶情绪也需要Trp通道。我们的初步结果首次表明，Ae.埃及伊蚊 显示出对FA的双峰吸引和厌恶。此外，Ae.埃及人为候选人编码同源基因 果蝇体内发现的FA受体。这项提案的目标将建立在Ae的初步调查结果的基础上。埃及伊蚊。 目标1的目标是确定影响叮咬和血液喂养的相关FA浓度的范围 天哪。并定义了味觉在控制双峰FA反应中的作用。在目标2中，我们将测试一下它的味道 对Ae的要求。埃及埃及色氨酸通道同源基因和候选GPCRs对 Fas.通过识别FA检测的受体机制，这项建议不仅提供了改善我们的 了解定义不清的昆虫味觉模式，但也要确定昆虫改良的特定目标 驱虫剂。

Abstract Mosquito bites are not simply an itchy annoyance- diseases spread through mosquito bites are a leading cause of morbidity and mortality each year and impose a heavy economic burden on healthcare systems around the world. When an insect disease vector lands on a host, it uses contact chemosensation, or taste, to inform its decision to bite and thereby spread disease. Insect repellants that function to disrupt sensation of taste cues, including DEET, have proven effective as antifeedants but are not without significant limitations. Many biting insects, including the dengue vector Aedes (Ae.)aegypti, show a greater reduction in biting and blood feeding when presented with fatty acids (FAs), the palatable component of dietary fats, than with DEET. In spite of findings like this, the receptor mechanisms employed in mosquito taste, including FA taste, are largely unknown and remain unexplored. Many taste modalities have been studied extensively in Drosophila melanogaster, which is a dipteran relative of Ae. aegypti, yet the molecular requirements for FA taste are unresolved. To this effect, we propose to employ our recent findings in the powerful model organism Drosophila to identify the currently unknown cellular and receptor mechanisms underlying FA taste in Ae. aegypti. In Drosophila, low concentrations of FAs are attractive, while high concentrations are aversive. In addition to recent evidence that gustatory attraction to low concentrations of FAs is conferred by a specific subset of gustatory receptor neurons (GRNs) and requires phospholipase C, data from our lab suggest requirements for a G-protein coupled receptor (GPCR) and a TRP channel. In addition to its role in attraction, the TRP channel is also required for aversion. Our preliminary results show for the first time that Ae. aegypti displays bimodal attraction and aversion to FAs. In addition, Ae. aegypti encodes homologs for the candidate FA receptors identified in Drosophila. The aims of this proposal will build on preliminary findings in Ae. aegypti. The goal of Aim #1 is to identify the range of relevant FA concentrations that impact biting and blood feeding in Ae. aegypti and define the role of taste in controlling the bimodal FA responses. In Aim #2 we will test the taste requirement for an Ae. aegypti TRP channel homolog and candidate GPCRs in attraction and aversion towards FAs. By identifying the receptor mechanisms for FA detection, this proposal offers to not only improve our understanding of a poorly defined insect taste modality but also to identify specific targets for improved insect repellants.