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

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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.