Physiology and Pathophysiology of Interactions between Hair Cells and Neurons.

毛细胞和神经元之间相互作用的生理学和病理生理学。

基本信息

批准号：
9280617
负责人：
Ulrich Mueller
金额：
$ 48.55万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-15 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9280617
关键词：
Adhesives Adult Affect Afferent Neurons Alleles Alternative Splicing Animal Model Auditory Catalytic Domain Cell physiology Cells Child Communication Complex Data Defect Development Disease Electrophysiology (science)Family Functional disorder Gene Mutation Genes Genetic Genetic Transcription Genetically Modified Animals Goals Hair Cells Health Hearing Hearing Impaired Persons Histology Homologous Gene Human In Situ Hybridization Individual Inner Hair Cells Knockout Mice Laboratories Labyrinth Mediating Membrane Transport Proteins Modeling Molecular Monomeric GTP-Binding Proteins Mus Mutant Strains Mice Mutation Neurites Neurons Orthologous Gene Outer Hair Cells Pathogenesis Pathway interactions Pattern Physiology Play Presbycusis Process Protein Isoforms Proteins Quality of life RNA Splicing RNA analysis Retina Role Sense Organs Sensorineural Hearing Loss Sensory Site Synaptic plasticity Testing Therapeutic Transcript Variant Vesicle aging population base cell type comparative deafness differential expression experimental study hearing impairment insight member novel protein complex public health relevance receptor ribbon synapse sound spatiotemporal spiral ganglion

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of my laboratory is to elucidate the mechanisms that regulate the development and function of the auditory sense organ and how inner ear defects cause hearing loss. We propose here to study the function of the Ig-superfamily member neuroplastin (Nptn) in the inner ear. Based on our preliminary data we hypothesize that Nptn regulates hair cell function and their interactions with sensory afferent neurons by mechanisms that are regulated by alternative splicing of the primary Nptn transcript. To test our hypothesis, we will: (i) determine the expression pattern and subcellular localization of Nptn isoforms in the inner ear; (ii) Study the consequences of inactivation of Nptn isoforms in hair cells and afferent neurons of the inner ear for hearing function; (iii) Determine the mechanisms by which Nptn isoforms carry out their function in hair cells and afferent neurons; (iv) determine the extent to which mutations in the gene encoding NPTN and its close homologues cause hearing impairment in humans. We anticipate that our findings will reveal novel insights into the mechanisms that regulate the function of hair cells and their innervating sensory afferent neurons, and how mutations in NPTN cause disease.

描述（由申请人提供）：我的实验室的长期目标是阐明调节听觉器官发育和功能的机制以及内耳缺陷如何导致听力损失。我们在此建议研究 Ig 的功能。 -内耳中的超家族成员神经塑蛋白 (Nptn) 根据我们的初步数据，我们发现 Nptn 通过初级选择性剪接调节的机制来调节毛细胞功能及其与感觉传入神经元的相互作用。为了检验我们的假设，我们将：（i）确定 Nptn 亚型在内耳中的表达模式和亚细胞定位；（ii）研究 Nptn 亚型在内耳毛细胞和传入神经元中失活的后果。用于听力功能；(iii) 确定 Nptn 亚型在毛细胞和传入神经元中发挥其功能的机制；(iv) 确定编码 NPTN 的基因的突变程度；我们预计我们的研究结果将揭示调节毛细胞及其支配感觉传入神经元功能的机制，以及 NPTN 突变如何导致疾病。