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Opsins as a new class of evolutionarily conserved taste receptors: Diversity Supplement for Pre-Doctoral Training

视蛋白作为一类新的进化保守味觉受体：博士前培训的多样性补充

基本信息

批准号：
10750801
负责人：
CRAIG MONTELL
金额：
$ 6.05万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA BARBARA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-01 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10750801
关键词：
Address Aedes Amino Acids Animals Behavior Behavioral Assay Biological Assay Blood CRISPR/Cas technology Catechin Cellular biology Chemicals Clustered Regularly Interspaced Short Palindromic Repeats Culicidae Data Dengue Detection Development Diet Disease Disease Vectors Drosophila genus Electrophysiology (science)Esthesia Evolution Family Female Flavonoids Fruit G-Protein-Coupled Receptors Genetic Goals Grapefruit Health Homologous Gene Human Image Impairment In Vitro Insecta Ligand Binding Ligands Light Mammals Modality Modeling Molecular Genetics Motivation Mus Mutagenesis Mutant Strains Mice Mutation Neurons Nutrient Nutritional Opsin Organ Partner in relationship Persons Photoreceptors Plants Poison Population Production Property Proteins Receptor Activation Receptor Cell Rhodopsin Role Specificity Taste Buds Taste Perception Testing Tongue Training Transgenic Organisms Vertebrate Photoreceptors Virus Visual System Vitamin A Work Yellow Fever ZIKA antagonist behavior test chromophore defined contribution detector dietary egg experience experimental study fascinate feeding fly genetic manipulation human disease improved in vitro Assay in vivo insect disease vector interest male member mutant pre-doctoral receptor response sugar tool transcriptome transcriptome sequencing vector

项目摘要

Abstract Opsins are classical G-protein coupled receptors, which for more than a century have been thought to function exclusively as light detectors. However, using Drosophila, we have uncovered multiple, light-independent roles for opsins including detection of bitter tastants. This discovery raises exciting questions, which we propose to address here. Do opsins only respond to bitter compounds, or do they function more broadly in taste sensation? Of particular interest, do opsins serve as taste receptors in other animals, including the mosquito, Aedes (Ae.) aegypti? This vector spreads viruses that cause dengue, yellow fever, and other diseases that afflict millions of people each year. Both male and female Aedes use taste to identify nectar and avoid toxic chemicals, while females use many senses to identify people for blood meals. However, the receptors required for mosquito taste are largely unknown. Another fascinating question is whether opsins serve as taste receptors in mammals. To address these questions, we propose to employ an extensive suite of approaches including electrophysiology, Ca2+ imaging, behavioral assays, cell biology, an in vitro receptor activation assay, and state-of-the art molecular genetics. We will also bring to bear our expertise in Drosophila taste, opsins, and our recent experience performing molecular genetics and behavior in Ae. aegypti and in the mouse. Aim 1 will define the role of a Drosophila opsin in amino acid taste, which in flies is a poorly understood taste modality. Attraction to amino acids increases if the flies are kept on an amino acid deficient diet. We outline experiments to define the contribution of the opsin to this dynamic change in amino acid appeal. We will also test the proposal that the opsin is activated directly by amino acids. Aim 2 will build on our preliminary data that two Ae. aegypti opsins are expressed in the major taste organ, and are required for sensing a flavonoid. The goals of this aim are to reveal the chemical specificity of these opsins in vitro and in vivo, determine whether they act independently or together, and identify the gustatory receptor neurons in which these opsins function. Aim 3 will characterize the roles of opsins in mammalian taste. This aim is supported by preliminary data showing that multiple mouse opsins are expressed in the mouse tongue, and are activated in vitro by bitter compounds, including a flavonoid for which there is no known receptor. In addition, we present preliminary data that the response to this flavonoid is impaired in the opsin mutant. We propose to test the hypothesis that this opsin functions broadly in sensing flavonoids, identify the taste receptor cells that express this and the other “gustatory opsins,” and perform behavioral tests with mutants to characterize the requirements for each opsin for sensing bitter compounds. The results from this project would establish opsins as a new class of taste receptor conserved from insects to mammals. We propose that defining opsins as the first bitter receptors in mosquitoes offers the potential to harness this information to manipulate mosquito behavior and thereby reduce their populations and thus insect-borne disease.

摘要