The role of CFAP69 in olfaction

CFAP69 在嗅觉中的作用

基本信息

批准号：
10394211
负责人：
HAIQING ZHAO
金额：
$ 33.77万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10394211
关键词：
Action Potentials Address Adenovirus Vector Affect Afferent Neurons Amino Acids Animal Behavior Animal Model Animals Attenuated Behavior Behavioral Biochemical Biology Brain Cells Chimeric Proteins Cilia Code Cues Electrophysiology (science)Exhibits Family Dasypodidae Fire - disasters Flagella Food Functional disorder Human Inferior Kinetics Knock-out Knockout Mice Knowledge Mass Spectrum Analysis Mediating Membrane Molecular Mus Mutant Strains Mice Mutation Nature Nose Odors Olfactory Epithelium Olfactory dysfunction Organism Output Pathway interactions Pattern Performance Peripheral Pharmacology Phase Phenotype Physiology Play Preparation Process Property Proteins Proteomics Protocols documentation Publications Quality of life Receptor Cell Research Role Sensory Sensory Receptors Signal Transduction Site Smell Perception Stimulus System Time base cohesion conditional knockout experimental study fitness in vivo mouse model mutant novel olfactory sensory neurons olfactory stimulus protein protein interaction response temporal measurement

项目摘要

Necessary steps towards understanding the sense of smell include characterizing the relevant molecular components that regulate olfactory sensory neuron (OSN) responses and analyzing behaviors of animal models that harbor abnormal odor coding. Our initial studies in mice suggest that Cilia- and Flagella-Associated Protein 69 (CFAP69), an evolutionarily conserved and poorly studied protein, plays a critical, yet unconventional, role in regulating olfactory transduction kinetics, odor stimuli coding of OSNs and also olfactory behavior. CFAP69 is enriched in OSN cilia, where olfactory signal transduction occurs. OSNs from CFAP69 conditional knockout mice display faster response kinetics in both on- and off- phases of the response with little change in response size, and can fire action potentials more faithfully to repeated stimuli than the control OSNs. CFAP69 conditional knockout mice, despite having higher temporal resolution in coding odor stimuli at the peripheral sensory neuron level, performed inferiorly in a challenging olfactory task. In this proposal, we will: 1) Determine the role of CFAP69 in regulating OSN sensitivity, adaptation and action potential coding by detailed electrophysiological analysis of odor responses at the levels of intact olfactory epithelium and isolated single cells from OSN-specific conditional knockout mice; 2) Investigate the mechanisms by which CFAP69 exerts its effect by using both a combined pharmacological and electrophysiological approach to determine the site of CFAP69 action in the transduction cascade and a biochemical approach to identify its interaction protein partners; and 3) Investigate how altered OSN response and odor stimuli coding affect olfactory behavior in OSN-specific conditional knockout mice. The proposed research will bring new knowledge and new perspective to the understanding of the olfactory transduction process, olfactory stimuli coding of OSNs and olfactory perception. The research will enhance our understanding of the fundamental biology of olfaction and olfactory dysfunction.

理解嗅觉的必要步骤包括表征相关的分子成分调节嗅觉感觉神经元（OSN）反应和分析具有异常的动物模型的行为气味编码。我们在小鼠中的最初研究表明，纤毛和鞭毛相关的蛋白69（CFAP69），一种进化。保守且研究不足的蛋白质在调节嗅觉转导动力学中起关键但非常规的作用， OSN的气味刺激编码以及嗅觉行为。 CFAP69在OSN Cilia中富含嗅觉信号发生转导。来自CFAP69有条件敲除小鼠的OSN显示出较快的反应动力学动力学响应的阶段几乎没有响应大小的变化，并且可以更忠实地发射动作潜力到重复的刺激比控制OSN。 CFAP69有条件的基因敲除小鼠，尽管在编码气味方面具有较高的时间分辨率在具有挑战性的嗅觉任务中，在周围感觉神经元水平下的刺激效果下降。在此提案中，我们将： 1）确定CFAP69在调节OSN灵敏度，适应和动作电位编码中的作用来自完整嗅觉上皮和分离的单个细胞的气味反应的电生理分析 OSN特异性有条件敲除小鼠； 2）研究CFAP69通过两者都使用其作用的机制一种合并的药理和电生理方法，用于确定转导中CFAP69作用的位点级联和一种生化方法来识别其相互作用蛋白伴侣的相互作用； 3）研究OSN响应如何改变和气味刺激编码会影响OSN特异性有条件敲除小鼠的嗅觉行为。拟议的研究将将新的知识和新观点带入对嗅觉转导过程的理解，嗅觉刺激 OSN和嗅觉的编码。这项研究将增强我们对嗅觉和嗅觉功能障碍。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Intravenous administration of multipotent stromal cells and bone allograft modification to enhance allograft healing.

DOI：
10.2217/rme-2018-0063
发表时间：
2019-02
期刊：
Regenerative medicine
影响因子：
2.7
作者：
Sharada Paudel;Wen-han Lee;Moses Lee;T. Zahoor;R. Mitchell;Shang-You Yang;Haiqing Zhao;L. Schon-
通讯作者：
Sharada Paudel;Wen-han Lee;Moses Lee;T. Zahoor;R. Mitchell;Shang-You Yang;Haiqing Zhao;L. Schon-