The molecular basis of fatty acid taste in Aedes aegypti

埃及伊蚊脂肪酸味道的分子基础

• 批准号: 10679953
• 负责人: Angela Elisa Morales
• 金额: $ 3.68万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-06 至 2025-02-05
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10679953
• 关键词: Aedes; Animals; Behavior; Behavioral; Behavioral Assay; Bite; Blood; Calcium; Cues; Culicidae; Data; Dengue; Desire for food; Detection; Dietary Component; Dietary Fats; Disease; Disease Vectors; Drosophila genus; Drosophila melanogaster; Economic Burden; Electrophysiology (science); Esthesia; Fatty Acids; Fatty acid glycerol esters; G-Protein-Coupled Receptors; Goals; Health; Healthcare Systems; Homologous Gene; Human; Image; In Vitro; Individual; Insect Bites; Insecta; Invertebrates; Mediating; Modality; Molecular; Molecular Target; Morbidity - disease rate; Mosquito-borne infectious disease; Natural Compound; Neurons; Opsin; Organ; Pain; Painless; Partner in relationship; Peripheral; Persons; Phospholipase; Phospholipase C; Play; Role; Sensory; Series; Skin; Source; TRP channel; Taste Perception; Testing; Time; Virus; egg; experimental study; feeding; improved; insect disease vector; insight; model organism; mortality; mutant; patch clamp; preference; receptor; response; sugar; taste system; transmission process; vector; vector control

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.

抽象的 蚊虫叮咬不仅仅是令人烦恼的瘙痒——通过蚊虫叮咬传播的疾病是主要的疾病 每年造成发病和死亡的原因，并给医疗保健系统带来沉重的经济负担 世界各地。当昆虫病媒落在宿主身上时，它会利用接触化学感觉或味觉来 告知其咬人的决定，从而传播疾病。驱虫剂的作用是扰乱感觉 味觉线索，包括避蚊胺，已被证明作为拒食剂是有效的，但也有很大的局限性。 许多叮咬昆虫，包括登革热媒介埃及伊蚊，叮咬和蚊虫叮咬次数均大幅减少。 与含有避蚊胺的脂肪酸（FA）（膳食脂肪的可口成分）相比，血液喂养更有效。 尽管有这样的发现，蚊子味觉（包括 FA 味觉）所采用的受体机制是 很大程度上是未知的，并且尚未被探索。果蝇的许多味觉模式已被广泛研究 黑腹果蝇 (melanogaster)，是伊蚊 (Ae) 的双翅目近亲。埃及伊蚊，但 FA 味道的分子要求是 未解决。为此，我们建议利用我们在强大的模型生物体中的最新发现 果蝇鉴定目前未知的 Ae 中 FA 味觉的细胞和受体机制。 埃及伊蚊。在果蝇中，低浓度的 FA 具有吸引力，而高浓度的 FA 则令人厌恶。在 最近的证据表明，低浓度 FA 的味觉吸引力是由特定的物质赋予的。 我们实验室的数据表明，味觉受体神经元 (GRN) 的子集需要磷脂酶 C G 蛋白偶联受体 (GPCR) 和 TRP 通道的要求。除了具有吸引人的作用外， TRP 通道也是厌恶所必需的。我们的初步结果首次表明 Ae。埃及伊蚊 对 FA 表现出双峰吸引力和厌恶。此外，艾. aegypti 编码候选者的同源物 在果蝇中鉴定出 FA 受体。该提案的目标将建立在 Ae 的初步调查结果之上。埃及伊蚊。 目标 1 的目标是确定影响咬合和血液喂养的相关 FA 浓度范围。 艾。 aegypti 并定义了味觉在控制双峰 FA 反应中的作用。在目标#2中，我们将测试味道 Ae 的要求。埃及伊蚊 TRP 通道同系物和候选 GPCR 对吸引和厌恶的影响 FA。通过确定 FA 检测的受体机制，该提案不仅可以改善我们的 了解不明确的昆虫味觉模式，同时确定改进昆虫的具体目标 驱虫剂。