TOP ＞ シンポジウム

シンポジウム 26 化学感覚の分子神経基盤：受容体の発見と進化、そして内受容へ 26 Molecular and neuronal mechanisms of chemoreception: from gustation to interoception 座長：樽野 陽幸（京都府立医科大学大学院医学研究科・細胞生理学）・Liman Emily R（Section of Neurobiology, University of Southern California） 2022年6月30日　14:00～14:24　沖縄コンベンションセンター 会議場B5～7　第4会場 1S04a-01 脊椎動物における甘味・旨味感覚の進化 Evolution of sweet and umami taste perception in vertebrates *戸田 安香(1) 1. 明治大学農学部 *Yasuka Toda(1) 1. Dept. Agric. Chem., Meiji University, Kanagawa, Japan Keyword: taste, umami, GPCR, evolution Sensory systems can evolve and adapt to new environmental niches. Taste perception plays an essential role in diet choice. Among five basic tastes (sweet, umami, bitter, salty, and sour), umami and sweet tastes are sensed by G protein-coupled receptors (GPCRs) termed T1Rs. Umami tastes are sensed by a heteromeric complex of T1R1 and T1R3, while sweet tastes are sensed by the T1R2 + T1R3 heterodimer. Retention of these receptors over timescales is shaped by feeding ecology. For example, some obligate carnivores, such as cats, lost T1R2, consistent with lack of sugars in their diet. Birds, which evolved from presumably carnivorous theropod dinosaurs, have also lost T1R2. However, we recently revealed that nectarivorous birds, such as hummingbirds and songbirds, have subsequently acquired the ability to detect sugars by changing the function of their T1R1/T1R3. Furthermore, by examining taste receptor response from representatives of all major primate lineages, we were able to track the evolution of the umami receptor responses and determine when the glutamate response, which is a characteristic of human T1R1/T1R3, evolved. We propose that insectivorous mammalian ancestors had a nucleotide-sensitive T1R1/T1R3 and that the multiple lineages of primates, including ancestors of humans, have evolved the umami taste receptor for detecting glutamate of their leafy diets. These findings shed new light on the adaptive radiation of vertebrates and helps reveal the genetic basis of dietary niche divergence. 2022年6月30日　14:24～14:48　沖縄コンベンションセンター 会議場B5～7　第4会場 1S04a-02 Proton channels and the molecular basis for sour taste *Emily Liman(1) 1. University of Southern California Keyword: gustatory, ion channel, acid-sensitive, sour taste The taste system allows animals to sample chemicals in their environment before ingestion to identify those that are nutritious and avoid others that are noxious. Sour, the taste of acids, has remained among the most mysterious of the basic taste qualities, its function unknown and the molecular nature of its receptor allusive. Acids are detected by type III taste receptor cells (TRCs), located in taste buds across the tongue and palate epithelium. The first step in sour taste transduction is believed to be the entry of protons into the cell cytosol which leads to cytosolic acidification and the generation of action potentials. To identify candidate receptors for sour taste, we previously performed an unbiased screen of genes enriched in type III TRCs, from which we identified Otop1 and showed that it encodes a novel proton-selective ion channel (OTOP1). To test whether OTOP1 is required for sour taste, we generated a knockout mouse strain with Crispr-cas9 (Otop1-KO). Type III TRCS from Otop1-KO mice showed a complete lack of the inward proton current and failed to fire actions potentials to acid stimuli. Gustatory nerve responses to citric acid and HCl applied to the tongue of Otop1-KO mice were severely and selectively attenuated. These data firmly establish OTOP1 as a bona fide receptor that is both necessary and sufficient for the gustatory responses to acid stimuli. The structure of OTOP1 revealed by CryoEM shows that it assembles as a dimer, that lacks a central permeation pathway. Current and ongoing experiments are aimed at understanding the functional properties of OTOP1 and their structural basis. 2022年6月30日　14:48～15:12　沖縄コンベンションセンター 会議場B5～7　第4会場 1S04a-03 Functional diversification of taste cells in mice *Ichiro Matsumoto(1) 1. Monell Chemical Senses Center, Philadelphia, PA, USA Keyword: taste cell Taste contributes to quality of life and our health, aiding with the recognition of nutrients and the detection of harmful substances in food. Sweet taste allows the recognition of carbohydrates by detecting sugars, and sour taste allows the recognition of pathogenic microorganisms in rotten foods by detecting acids. Mice have five subsets of taste cells that detect substances human perceive sweet, umami, bitter, salty, and sour, because they express taste receptors in 5 specific subsets of taste cells, each of which is dedicate to evoke one taste out of 5 basic tastes. Several lines of studies indicate that T1R1-absent T1R3-expressing (i.e., T1R1-T1R3+) cells mediate sweet taste. Intriguingly, however, there is micro-diversity in T1R1-T1R3+ taste cells based on their molecular features, whereas T1R1+T1R3+ umami taste cells are a unique subset. We’ll introduce our recent findings and discuss about the possibility that mice have more variety of taste cells than expected. 2022年6月30日　15:12～15:36　沖縄コンベンションセンター 会議場B5～7　第4会場 1S04a-04 Sensory Mechanisms of the Mammalian Airways *Sara Prescott(1) 1. Massachusetts Institute of Technology, Cambridge, MA, USA Keyword: vagal neurons, airway defense, laryngeal taste buds, cough Breathing is essential for life, yet the neural mechanisms by which the body senses cues from the airways remain poorly understood. By combining physiology, mouse genetics and molecular neuroscience techniques, we investigated how airway insults are detected to elicit adaptive reflexes that safeguard respiration. First, we charted the diversity of airway-innervating neurons by single cell transcriptome profiling of mouse vagal ganglia. We observed a surprising diversity (>37 subtypes) of vagal afferents that project to the airways and viscera. To explore their role in respiratory homeostasis, we curated a library of Cre driver mice that broadly encompass our vagal atlas and used genetically-guided tracing, ablations and optogenetics to pinpoint a rare population of throat-innervating neurons (∼100 neurons/mouse) that guard the airways against assault. These neurons, marked by P2RY1, are required for water and acid-evoked airway protective reflexes like cough and pharyngeal swallowing. Targeted tracing revealed that P2RY1 neurons directly appose chemosensory cells in the larynx resembling classic taste buds. Ablation of P2RY1 neurons or genetic deletion of purinergic receptors abolished water-evoked laryngeal responses, revealing a novel circuit that serves as a general alarm system against inappropriate aspiration. Overall our work provides mechanistic insights into the neural basis of airway defense, and offers a general molecular/genetic roadmap for internal organ sensation by the vagus nerve. 2022年6月30日　15:36～16:00　沖縄コンベンションセンター 会議場B5～7　第4会場 1S04a-05 Extraoral distribution and function of the channel synapse *Akiyuki Taruno(1,2,3) 1. Grad School Med Sci, Kyoto Pref Univ Med, Kyoto, Japan, 2. JST CREST, 3. JST PRESTO Keyword: synapse, CALHM, ATP, interception Among members of the calcium homeostasis modulator (CALHM) family, CALHM1 was originally identified as a pore-forming subunit of a slowly-activating voltage-gated channel with a wide pore that is permeable to adenosine triphosphate (ATP). Subsequently, a hetero-oligomer of CALHM1 and CALHM3, also referred to as CALHM1/3, was discovered as a fast-activating voltage-gated ATP-permeable channel. CALHM1/3 channels are expressed in taste bud cells where they mediate the action potential-dependent release of neurotransmitter ATP toward the afferent neurons, and consequently the perception of tastes. Remarkably, instead of synaptic vesicles, taste bud cells employ a noncanonical chemical synapse involving an ion channel pore as the conduit for neurotransmitter release. As chemical neurotransmission has been supposed to be mediated solely by Ca2+-dependent exocytosis, this unique chemical synapse is termed “channel synapse”. Although the physiological relevance of the channel synapse in gustation has been clarified, it remains unknown where else the synapse exists and functions outside the tongue. Here, we generated a reporter mouse model for Calhm1 and Calhm3, screened over 40 organs for reporter protein expression, and revealed tissue distribution of cells expressing CALHM1/3. In one of those CALHM1/3+ tissues, we genetically, anatomically, and functionally identified the presence of channel synapses and its physiological relevance. Extra-oral distribution and function of the CALHM channel synapse will be discussed.