Characterization of Ionotropic Receptors in Mating and Blood Feeding in Anopheles mosquitoes

项目摘要 携带疾病的蚊子的交配、寻找宿主和吸血行为是由一种 一系列化学感受和进食的附属物，对传播周期至关重要。为了找到交配对象 伴侣或区分主机气味线索（利它素）从许多其他环境刺激，按蚊 coluzzii蚊子使用敏锐的嗅觉/味觉，依赖于至少三个大的化学感觉家族。 受体：这些是味觉（AcGrs）、气味（AcOrs）和变体离子型（AcIrs）受体， 表达在外周化学感受组织中，并将化学环境的信息传递给 个脑袋与高度分歧和相对充分研究的AcOr家族相反，化学感受器的AcIr家族 很大程度上是保守的，相对来说知之甚少。 我们小组利用最先进的转基因报告基因和基因靶向方法进行的初步研究 已经开始探索专性IR共受体三联体之一AcIr 76 b的表达和功能。这些 研究证实了广泛的表达谱，更重要的是，已经开始阐明 IR信号在介导对许多气味线索的反应中起作用，这些气味线索是蚊子重要行为的基础，例如 交配和寻找宿主/吸血。这使我们假设AcIrs在神经元细胞中起着关键作用。 对尚未确定的交配和吸血线索的敏感性，以及几种成熟的人类皮肤 成虫触角、下颚须、唇瓣和跗上的感受器中的气味物质。例如，凹槽- PEG感受器对重要的人源利它素-如氨、乳酸和 丁胺-但其中的神经元表达AcIr 76 b和其他AcIrs，但不表达AcOrs。在这 建议，我们试图全面阐明AcIrs的分子功能及其潜在的作用， 宿主利它素、交配和供血受体，从而阐明化学感受器的关键成分。 疟疾媒介蚊子中的过程。猫猴。拓宽了我们对寻找宿主的理解，血- 摄食和交配生物学。coluzzii和其他传播疾病的蚊子， 保存得非常好，可能对人类健康有重要的未来意义，因为它提供了新的方法， 阻止疾病传播。

Project Summary Mating, host-seeking and blood-meal-acquisition behaviors in disease-carrying mosquitoes are facilitated by an array of chemosensory and feeding appendages that are critical for transmission cycles. In order to find a mating partner or distinguish host odor cues (kairomones) from numerous other environmental stimuli, Anopheles coluzzii mosquitoes use a keen sense of smell/taste that relies on at least three large families of chemosensory receptors: these are the gustatory (AcGrs), odorant (AcOrs) and variant ionotropic (AcIrs) receptors that are expressed in peripheral chemosensory tissues and convey information about the chemical environment to the brain. In contrast to the highly divergent and relatively well-studied AcOr family, the AcIr family of chemoreceptors is largely conserved and relatively poorly understood. Preliminary studies from our group utilizing state-of-the-art transgenic reporters and gene-targeting approaches have begun to explore the expression and function of AcIr76b, one of the triad of obligate IR co-receptors. These studies confirm broad expression profiles and, more importantly, have begun to elucidate the essential role that IR signaling plays in mediating responses to many odor cues that underlie important mosquito behaviors, such as mating and host seeking/blood feeding. This has led us to hypothesize that AcIrs play a critical role in neuronal sensitivity to as-yet undefined mating and blood-feeding cues as well as several well-established human skin odorants in sensilla that reside on the adult antennae, maxillary palps, labella, and tarsi. For example, grooved- peg sensilla are responsive to important human-derived kairomones—such as ammonia, lactic acid and butylamine—yet the neurons housed within them express AcIr76b and other AcIrs but not AcOrs. In this proposal, we seek to comprehensively elucidate the molecular functionality of AcIrs and their potential roles as host kairomone, mating and blood-feeding receptors and thus clarify key components of the chemosensory processes in the malaria vector mosquito An. coluzzii. Broadening our understanding of the host-seeking, blood- feeding, and mating biology of An. coluzzii and indeed other disease-transmitting mosquitoes in which Irs are extremely well conserved may have important future implications for human health by providing new ways to interfere with disease transmission.