Functions of Myosin VII in Mechanosensory Hair Cells

肌球蛋白 VII 在机械感觉毛细胞中的功能

基本信息

批准号：
9027704
负责人：
Peter Gordon Barr-Gillespie
金额：
$ 62.91万
依托单位：
OREGON HEALTH & SCIENCE 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：
2015-12-01 至 2020-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9027704
关键词：
Actins Adhesions Affect Alleles Ankle Antibodies Auditory CDH23 gene Carrier Proteins Cell physiology Cellular biology Chickens Child Collaborations Complementary DNA Complex Data Defect Development Disease Disease Outcome Ethylnitrosourea Functional disorder Gene Mutation Genes Genetic Goals Hair Hair Cells Health Hearing Impaired Persons Hereditary Disease House mice Human Immunoprecipitation Impairment Individual Knock-out Laboratories Lateral Lead Length Letters Link MYO7A gene Mass Spectrum Analysis Mediating Methods Molecular Molecular Biology Morphogenesis Motor Mus Mutation Myosin ATPase Names PCDH15 gene Pathway interactions Physiology Play Positioning Attribute Presbycusis Process Proteins Proteomics Publishing Quality of life Rest Role Shotguns Signal Transduction Specific qualifier value Stereocilium Testing Transcript Usher Syndrome, Type 1C Usher Syndrome, Type 1G aging population base cellular transduction chemical genetics deafness density hearing impairment loss of function mutant novel polymerization protein complex public health relevance research study sound spelling vibration web site

项目摘要

Project Summary The long-term goal of our laboratories is to elucidate the mechanisms that control hair cell development and function, and ascertain the defects in this process that cause deafness. We propose here to identify and study proteins that physically and functionally interact with MYO7A and therefore mediate its function in hair cells. Based on published and preliminary data, we hypothesize that MYO7A has a three-fold function in hair cells, regulating the transport of proteins critical for hair bundle adhesion and actin polymerization and directly controlling mechanotransduction. To test our hypothesis, we will: (i) define the protein complexes that mediate stereocilia adhesion, focusing on those consisting of PCDH15 and GRP98; (ii) determine how MYO7A complexes regulate stereocilia length, focusing initially on the complex with CAPZ that we have defined; (iii) specify how MYO7A and its interacting proteins control mechanotransduction. Our preliminary data show the feasibility of our approach. We have already identified hair bundle proteins that interact with MYO7A and mediate its function. We anticipate that some of the novel interaction partners of MYO7A will be affected in genetic diseases that cause hearing impairment.

项目概要我们实验室的长期目标是阐明控制毛细胞发育和毛细胞发育的机制。功能，并确定该过程中导致耳聋的缺陷。我们在这里建议识别和研究与 MYO7A 发生物理和功能相互作用的蛋白质，从而介导其在毛细胞中的功能。根据已发表的初步数据，我们假设 MYO7A 在毛细胞中具有三重功能，调节对发束粘附和肌动蛋白聚合至关重要的蛋白质的运输，并直接控制力传导。为了检验我们的假设，我们将：（i）定义介导的蛋白质复合物静纤毛粘附，重点关注由 PCDH15 和 GRP98 组成的粘附； (ii) 确定MYO7A如何复合物调节静纤毛长度，首先关注我们定义的 CAPZ 复合物； (三) 详细说明 MYO7A 及其相互作用蛋白如何控制机械转导。我们的初步数据显示我们的方法的可行性。我们已经鉴定出与 MYO7A 相互作用的发束蛋白介导其功能。我们预计 MYO7A 的一些新型相互作用伙伴将受到影响导致听力障碍的遗传性疾病。