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

按蚊交配和吸血中离子型受体的表征

• 批准号: 10736638
• 负责人: LAURENCE J ZWIEBEL
• 金额: $ 49.32万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-02 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736638
• 关键词: Address; Adult; Afferent Neurons; Aldehydes; Amines; Ammonia; Anopheles Genus; Arboviruses; Behavior; Behavioral; Behavioral Assay; Biological Assay; Biology; Blood; Brain; CRISPR/Cas technology; Carboxylic Acids; Chemicals; Chemoreceptors; Complex; Cues; Culicidae; Data; Dengue; Disease; Electrodes; Electrophysiology (science); Environment; Etiology; Family; Family member; Female; Filariasis; Future; Gene Targeting; Hand; Health; Human; Human Bites; Imines; In Situ Hybridization; Individual; Intervention; Kairomones; Knock-in; Lactic acid; Larva; Malaria; Maps; Maxilla; Mediating; Molecular; Mosquito-borne infectious disease; Neurons; Odors; Oocytes; Partner in relationship; Peripheral; Phenotype; Pheromone; Phylogenetic Analysis; Physiological; Play; Population Sizes; Public Health; Receptor Gene; Reporter Genes; Research; Role; Semiochemicals; Sensory; Sensory Process; Sensory Receptors; Signal Transduction; Skin; Smell Perception; Stimulus; System; Taste Perception; Tissues; Transgenic Organisms; Variant; Vectorial capacity; Volatilization; Xenopus laevis; ZIKA; adult nutrition; appendage; base; design; disease transmission; feeding; improved; in vivo; loss of function; malaria transmission; mutant; neurogenetics; novel; olfactory receptor; preference; programs; receptor; response; sensory mechanism; transcriptome; transmission process; vector; vector control; vector mosquito; voltage clamp

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.

项目摘要 携带疾病的蚊子的交配、寻找宿主和获取血液的行为是由一种 一系列对传播周期至关重要的化学传感器和喂养附件。为了找到交配对象 将宿主气味线索(凯洛酮)与许多其他环境刺激(按蚊)配对或区分开来 蚊子使用敏锐的嗅觉/味觉，这依赖于至少三个大的化学感官家族。 受体：这些是味觉(AcGrs)、气味(Acors)和变异型离子亲和性(Acirs)受体，它们是 在外周化学感觉组织中表达，并将有关化学环境的信息传递给 大脑。与高度分化和研究相对较好的Acor家族不同，ACIR家族的化学受体 在很大程度上是保守的，相对较少被理解。 我们小组利用最先进的转基因记者和基因打靶方法进行的初步研究 已经开始探索专性IR辅受体三联体之一的Acir76b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信号在调节对许多气味线索的反应中发挥作用，这些气味线索是重要蚊子行为的基础，例如 作为交配和寻找寄主/吸血。这导致我们假设Acirs在神经元中起着关键作用 对尚不明确的交配和觅血暗示以及几种成熟的人类皮肤的敏感性 感受器中的气味，存在于成虫的触角、上颌触须、拉贝拉和鞑靼上。例如，凹槽- 佩格感受器对重要的人类来源的凯洛酮有反应--如氨、乳酸和 丁胺-然而，它们内部的神经元表达Acir76b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 宿主激动素、交配和供血受体，从而阐明化学感受器的关键成分 疟疾媒介蚊子和蚊子中的过程。猫头鹰。拓宽了我们对寻找宿主的理解，血液- 食性和交配生物学。Coluzzii和其他传播疾病的蚊子，IRS在其中 极好的保守性可能会对人类健康产生重要的未来影响，因为它提供了新的方法 干扰疾病传播。