VOLTAGE-DEPENDENT ION CHANNELS IN GUSTATION

味觉中电压相关的离子通道

基本信息

批准号：
8071083
负责人：
LIQUAN HUANG
金额：
$ 31.08万
依托单位：
MONELL CHEMICAL SENSES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-14 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8071083
关键词：
Afferent Neurons Ageusia Animals Behavioral Behavioral tic Biochemical Biochemistry Bioinformatics Biological Assay Brain Calcium Calcium Channel Cell membrane Cells Code Coupled Cranial Nerves Development Dominant-Negative Mutation Dyes Dysgeusia Electrical Synapse Electrophysiology (science)Esthesia Event Functional Magnetic Resonance Imaging G Protein-Coupled Receptor Genes GTP-Binding Proteins Genes Genetic Human Genome Hypogeusia Ion Channel KCNQ1 protein Knock-out Knockout Mice Knowledge Label Lead Length Literature Mediating Membrane Membrane Potentials Methods Modality Molecular Molecular Biology Molecular Cloning Molecular and Cellular Biology Monitor Monovalent Cations Nerve Nerve Fibers Neuraxis Neurons Organ PHluorin Pathway interactions Perception Peripheral Physiological Process Property Protein Isoforms Protein Subunits Proteins RNA Interference RNA Splicing Receptor Cell Receptor Signaling Research Research Personnel Role Signal Transduction Signal Transduction Pathway Signaling Molecule Site Small Interfering RNA Sodium Chloride Stimulus Surface Synapses Synaptic Transmission Synaptic Vesicles TRPM5 gene Taste Bud Cell Taste Buds Taste Disorders Taste Perception Techniques Testing Variant Wild Type Mouse afferent nerve base behavior test cell type channel blockers desensitization effective therapy insight loss of function mouse genome mutant novel overexpression paracrine programs receptor relating to nervous system response tongue papilla transmission process voltage

项目摘要

DESCRIPTION (provided by applicant): Taste perception is initiated by the interaction of sapid molecules with proteins on the surface of taste bud cells. These gustatory signals are subsequently transduced, processed in taste buds, coded and transmitted by cranial nerves to the brain. The long-term objective of our research program is to molecularly identify and functionally characterize key proteins that are involved in taste signal transduction and coding in taste buds, and decoding in the central nervous system, and eventually to reconstruct the molecular events of taste sensation and perception. We have used molecular cloning and functional analyses to identify and characterize a number of taste transduction components, including a G-protein coupled taste receptor T1R3, G protein subunits and a transient receptor potential ion channel TRPM5. In order to understand the molecular events downstream of TRPM5 and to reveal ion channels that are responsible for sour and salty tastes, we have determined the expression of six voltage-dependent calcium channels in taste bud cells. The specific aims of this proposal are: 1) to identify and colocalize voltage-dependent calcium channel subunits with known taste signaling molecules in taste bud cells; 2) to heterologously express and functionally characterize novel isoforms of these voltage-dependent calcium channels isolated from taste buds; 3) to determine possible roles of these voltage-dependent calcium channels in taste bud synaptic transmission by monitoring the effect of pharmacological and genetic perturbation of these channels on the elevation of intracellular calcium concentrations and synaptic activity in taste bud cells in response to taste stimuli; 4) finally, to determine possible roles of these voltage-dependent calcium channels in taste sensation by gustatory nerve recording and animal behavioral tests with mutant animals. The results of these studies will yield new insights into the molecular mechanisms underling sour, salt, bitter, sweet and umami taste transduction, synaptic transmission and peripheral coding in the end organs of taste. The knowledge gained from this endeavor will further our understanding of the molecular bases of taste disorders such as malgeusia, dysgeusia, hypogeusia and ageusia and may lead to effective treatment.

描述（由申请人提供）：味觉感知是由糖化芽细胞表面上的汁液分子与蛋白质的相互作用引发的。这些味道信号随后被转导，在味蕾中处理，由颅神经编码和传播到大脑。我们的研究计划的长期目标是分子识别并在功能上表征与味觉转导和味蕾中涉及的关键蛋白质，并在中枢神经系统中解码，并最终重建味觉感觉和感知的分子事件。我们已经使用了分子克隆和功能分析来识别和表征许多味道转导成分，包括G蛋白偶联的味觉受体T1R3，G蛋白亚基和瞬时受体电位离子电池通道TRPM5。为了了解TRPM5下游的分子事件并揭示了负责酸和咸味的离子通道，我们已经确定了味蕾细胞中六个电压依赖性钙通道的表达。该提案的具体目的是：1）识别和将依赖电压依赖性的钙通道亚基与味蕾细胞中的已知味觉信号分子相结合； 2）异源表达并在功能上表征这些电压依赖性钙通道的新型同工型； 3）通过监测这些通道的药理和遗传扰动对味觉刺激的药理学和遗传扰动对这些通道对细胞内钙浓度和突触细胞中突触细胞中的抬高的药理和遗传扰动的影响，确定这些电压依赖性钙通道的可能作用； 4）最后，通过使用突变动物进行味觉神经记录和动物行为测试来确定这些电压依赖性钙通道的可能作用。这些研究的结果将产生对酸，盐，苦，甜和鲜味转导的分子机制的新见解。从这项工作中获得的知识将进一步了解我们对味觉疾病的分子碱基，例如麦物菌，de症，缺乏症和年龄，并可能导致有效的治疗。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Local microenvironment provides important cues for cell differentiation in lingual epithelia.

DOI：
10.1371/journal.pone.0035362
发表时间：
2012
期刊：
PloS one
影响因子：
3.7
作者：
Li F;Zhou M
通讯作者：
Zhou M

Conditional expression of the dominant-negative TGF-β receptor type II elicits lingual epithelial hyperplasia in transgenic mice.

显性失活 TGF-β 受体 II 型的条件表达引起转基因小鼠舌上皮增生。

DOI：
10.1002/dvdy.23933
发表时间：
2013
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
0
作者：
Li,Feng;Zhou,Mingliang
通讯作者：
Zhou,Mingliang

NTPDase2+ Cells Generate Lingual Epithelia and Papillae.

NTPDase2 细胞产生舌上皮和乳头。

DOI：
10.3389/fgene.2012.00255
发表时间：
2012
期刊：
Frontiers in genetics
影响因子：
3.7
作者：
Li,Feng;Cao,Jie;Zhou,Mingliang
通讯作者：
Zhou,Mingliang

Heterotrimeric G protein subunit Gγ13 is critical to olfaction.

DOI：
10.1523/jneurosci.5563-12.2013
发表时间：
2013-05-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Li F;Ponissery-Saidu S;Yee KK;Wang H;Chen ML;Iguchi N;Zhang G;Jiang P;Reisert J;Huang L
通讯作者：
Huang L

Sarco/Endoplasmic reticulum Ca2+-ATPases (SERCA) contribute to GPCR-mediated taste perception.