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Electrophysiological basis of sour taste transduction

酸味转导的电生理基础

基本信息

批准号：
10627899
负责人：
Sue C. Kinnamon
金额：
$ 47.96万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10627899
关键词：
Acids Action Potentials Animals Applications Grants Behavior Behavior assessment Behavioral Brain region Brown Fat Calcium Cell Separation Cells Circumvallate Papilla Citrus Fruit Cytosol Data Defect Detection Development Diabetes Mellitus Diet Disease Electrophysiology (science)Epithelium Exhibits Family Fire - disasters Food Funding Fungiform Papilla Gene Expression Profile Gene Family Genes Goals Homologous Gene Human Hypertension In Situ Hybridization Integral Membrane Protein Investigation Ion Channel Ions Knock-out Knockout Mice Laboratories Maintenance Mammals Measures Mediating Membrane Modeling Molecular Mouse Strains Mus Mutate Nature Nerve Obesity Operant Conditioning Palate Physiological Physiological Processes Play Potassium Channel Property Protein Isoforms Protons Receptor Cell Reporter Role Salts Sensory Signal Transduction Sodium Chloride Stimulus Sweetening Agents System Taste Buds Taste Perception Testing Tongue Type III Epithelial Receptor Cell Xenopus oocyte cell type combat defined contribution dietary experimental study genetic testing immunocytochemistry improved in vivo lipid metabolism member novel patch clamp promoter receptor receptor function response screening sensor taste stimuli taste system taste transduction

项目摘要

Project Summary The broad goal of the proposed experiments is to identify key molecules that allow mammals to detect basic tastes and generate electrical responses that are conducted to brain regions. Molecular mechanisms of taste reception have been a subject of intense investigation over the last 30 years, with great strides made in identifying receptors for bitter, sweet and umami. Much less is known about the nature and function of receptors for sour, the taste that allows us to detect acids in spoiled foods or citrus fruits. In this proposal, we will begin to unravel this problem as we test the contribution of the newly discovered otopetrin proton channels in the transduction of acidic and ionic tastes. These experiments build on the progress made in the last grant application, where we used a combination of cellular, molecular and functional approaches to identify the pH sensitive ion channels in Type III taste receptor cells (TRCs) that mediate sour taste. Notably, we described a novel proton-selective ionic current that is likely to be a key component of sour taste transduction. In the last funding period, we successfully identified the gene that encodes the proton channel, through functional screening of genes enriched in Type III TRCs. Among 41 genes tested, we identified one, encoding the transmembrane protein Otop1 that upon expression induced a proton current in both Xenopus oocytes and HEK-293 cells. Interestingly, Otop1 was first identified as a gene mutated in mice with vestibular defects (“tilted” or tlt) but its function in the vestibular system and elsewhere in the body was not understood. Building on these new results, we propose three specific aims to test the role of the Otop channels in taste signaling. The first aim will examine the functional distribution of Otop1 across the tongue and palate epithelium, allowing us to answer the question of whether Otop1 is the sole ion channel mediating proton influx in the gustatory system. In the second aim, we will measure cellular responses to acids in wildtype and Otop1 KO mice in order to determine the degree to which Otop1 contributes to sensory responses, ex vivo. In the third aim, we will measure responses from gustatory nerves and assess behavioral thresholds for acid detection in wildtype and Otop1 KO mice to determine the extent to which Otop1 mediates responses to sour taste stimuli in vivo. Together our experiments will allow us to determine if Otop1 functions as a sour taste receptor. Our efforts to identify mechanisms of taste transduction may allow the development of taste modifiers that can be used to enhance palatability of food, reducing the need to add sweeteners that contribute to the development of diabetes or salts that contribute to hypertension. Moreover, the proposed experiments will provide basic information regarding the functional properties of this new family of proton channels that will help us understand their contributions to diverse physiological processes, including brown fat metabolism and the development and maintenance of the vestibular system.

项目总结

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Activation Stoichiometry and Pore Architecture of TRPA1 Probed with Channel Concatemers.

DOI：
10.1038/s41598-018-35435-y
发表时间：
2018-11-20
期刊：
Scientific reports
影响因子：
4.6
作者：
Ye W;Tu YH;Cooper AJ;Zhang Z;Katritch V;Liman ER
通讯作者：
Liman ER

The evolution of sour taste.

DOI：
10.1098/rspb.2021.1918
发表时间：
2022-02-09
期刊：
Proceedings. Biological sciences
影响因子：
0
作者：
Frank HER;Amato K;Trautwein M;Maia P;Liman ER;Nichols LM;Schwenk K;Breslin PAS;Dunn RR
通讯作者：
Dunn RR

The proton channel OTOP1 is a sensor for the taste of ammonium chloride.

DOI：
10.1038/s41467-023-41637-4
发表时间：
2023-10-05
期刊：
NATURE COMMUNICATIONS
影响因子：
16.6
作者：
Liang, Ziyu;Wilson, Courtney E.;Teng, Bochuan;Kinnamon, Sue C.;Liman, Emily R.
通讯作者：
Liman, Emily R.

Structural motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels.

DOI：
10.7554/elife.77946
发表时间：
2022-08-03
期刊：
ELIFE
影响因子：
7.7
作者：
Teng, Bochuan;Kaplan, Joshua P.;Liang, Ziyu;Krieger, Zachary;Tu, Yu-Hsiang;Burendei, Batuujin;Ward, Andrew B.;Liman, Emily R.
通讯作者：
Liman, Emily R.

TRP Channels: Pain enters through the side door.

TRP通道：疼痛从侧门进入。