Characterization of the Mechanotransduction complex in hair cells
毛细胞中机械转导复合物的表征
基本信息
- 批准号:9901377
- 负责人:
- 金额:$ 33.26万
- 依托单位:
- 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:2015-04-01 至 2021-03-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAnimal ModelApicalAuditoryBindingBinding ProteinsBiochemicalBirdsCDH23 geneCadherinsCell physiologyCo-ImmunoprecipitationsCollectionComplexCoupledDominant-Negative MutationFamilyFamily memberFilamentFish ProteinsFishesFunctional disorderGenesGeneticGoalsHairHair CellsHearingHumanImmunoblottingIndividualInvestigationKnowledgeLabyrinthLeadLesionLinkMammalsMass Spectrum AnalysisMechanicsMediatingMembraneMembrane ProteinsMethodsModelingMolecularMouse ProteinMusMutationPCDH15 genePhenotypePlayPreparationProtein IsoformsProteinsSensory HairSensory ReceptorsSignal TransductionSpecificitySpeedStructureTransgenic OrganismsTwo-Hybrid System TechniquesUbiquitinUsher SyndromeVertebratesVestibular Hair CellsWorkYeastsZebrafishbasedeafnessdesignexperimental studyextracellularfollow-upgain of functionhearing impairmentin vivoin vivo imaginginsightlateral linelink proteinloss of functionmechanotransductionmembermutantnoveloverexpressionprotein functionpublic health relevancesoundyeast two hybrid system
项目摘要
DESCRIPTION (provided by applicant): Mutations in Protocadherin 15 (PCDH15) cause deafness in fish, mice, and humans. As a central and conserved component of the mechanotransduction complex in sensory hair cells, this unusual cadherin forms part of the extracellular filaments at the tips of stereocilia. These so-called `tip links' are thought to gate
mechanically sensitive channels. To gain a better understanding of how PCDH15 is coupled to the mechanotransduction machinery, we performed an unbiased molecular screen using zebrafish Pcdh15a as bait in a membrane-based yeast two-hybrid screen. We identified a positive interaction with Tmc2a, an orthologue of mammalian TMC2. Tmc2 was recently implicated in deafness and vestibular dysfunction in mice, and its closely related gene, Tmc1, is associated with both recessive and dominant forms of hearing loss in mice and humans (DFNA36 and DFNB7/11). Our preliminary results recapitulate the protein interactions found in the screen among both the zebrafish and mouse TMC and PCDH15 orthologues. In addition, we have discovered both loss-of-function and gain-of-function effects on hair-cell mechanosensitivity upon overexpression of fragments of Tmc2a in wild-type fish. Together, the link to Pcdh15 and the dominant negative or activating effects in hair cells provide compelling evidence that Tmc1/2 proteins are central players of the mechanotransduction complex in hair cells. We will characterize the interaction of Pcdh15 with Tmc1/2 proteins with genetic and biochemical methods, and study structure/function aspects of the complex in vivo. This work will increase our knowledge of the molecular basis of mechanotransduction and the understanding of how lesion of Tmc1 leads to hearing loss.
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The genetics of hair-cell function in zebrafish.
- DOI:10.1080/01677063.2017.1342246
- 发表时间:2017-09
- 期刊:
- 影响因子:1.9
- 作者:Nicolson T
- 通讯作者:Nicolson T
Zebrafish: from genes and neurons to circuits, behavior and disease.
斑马鱼:从基因和神经元到电路、行为和疾病。
- DOI:10.1080/01677063.2017.1359589
- 发表时间:2017
- 期刊:
- 影响因子:1.9
- 作者:Chandrasekhar,Anand;Guo,Su;Masai,Ichiro;Nicolson,Teresa;Wu,Chun-Fang
- 通讯作者:Wu,Chun-Fang
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Teresa A Nicolson其他文献
Teresa A Nicolson的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Teresa A Nicolson', 18)}}的其他基金
Neural defects in zebrafish auditory/vestibular mutants
斑马鱼听觉/前庭突变体的神经缺陷
- 批准号:
10412441 - 财政年份:2021
- 资助金额:
$ 33.26万 - 项目类别:
Molecular Analysis of Tmie in sensory hair cells
感觉毛细胞中 Tmie 的分子分析
- 批准号:
10395471 - 财政年份:2018
- 资助金额:
$ 33.26万 - 项目类别:
Molecular Analysis of Tmie in sensory hair cells
感觉毛细胞中 Tmie 的分子分析
- 批准号:
9901368 - 财政年份:2018
- 资助金额:
$ 33.26万 - 项目类别:
Characterization of the mechanotransduction complex in hair cells
毛细胞中机械转导复合物的表征
- 批准号:
9246481 - 财政年份:2015
- 资助金额:
$ 33.26万 - 项目类别:
Characterization of the mechanotransduction complex in hair cells
毛细胞中机械转导复合物的表征
- 批准号:
8885946 - 财政年份:2015
- 资助金额:
$ 33.26万 - 项目类别:
In vivo biotinylation for analysis of nuclear and protein dynamics
用于核和蛋白质动力学分析的体内生物素化
- 批准号:
8685235 - 财政年份:2013
- 资助金额:
$ 33.26万 - 项目类别:
In vivo biotinylation for analysis of nuclear and protein dynamics
用于核和蛋白质动力学分析的体内生物素化
- 批准号:
8546558 - 财政年份:2013
- 资助金额:
$ 33.26万 - 项目类别:
In vivo biotinylation for analysis of nuclear and protein dynamics
用于核和蛋白质动力学分析的体内生物素化
- 批准号:
8874954 - 财政年份:2013
- 资助金额:
$ 33.26万 - 项目类别:
In vivo biotinylation for analysis of nuclear and protein dynamics
用于核和蛋白质动力学分析的体内生物素化
- 批准号:
9093769 - 财政年份:2013
- 资助金额:
$ 33.26万 - 项目类别:
Genetic and molecular dissection of hair-cell function
毛细胞功能的遗传和分子解剖
- 批准号:
7065152 - 财政年份:2004
- 资助金额:
$ 33.26万 - 项目类别:
相似海外基金
Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
- 批准号:
495434 - 财政年份:2023
- 资助金额:
$ 33.26万 - 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
- 批准号:
10642519 - 财政年份:2023
- 资助金额:
$ 33.26万 - 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
- 批准号:
10586596 - 财政年份:2023
- 资助金额:
$ 33.26万 - 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
- 批准号:
10590479 - 财政年份:2023
- 资助金额:
$ 33.26万 - 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
- 批准号:
23K06011 - 财政年份:2023
- 资助金额:
$ 33.26万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
- 批准号:
10682117 - 财政年份:2023
- 资助金额:
$ 33.26万 - 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
- 批准号:
10708517 - 财政年份:2023
- 资助金额:
$ 33.26万 - 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
- 批准号:
10575566 - 财政年份:2023
- 资助金额:
$ 33.26万 - 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
- 批准号:
23K15696 - 财政年份:2023
- 资助金额:
$ 33.26万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
- 批准号:
23K15867 - 财政年份:2023
- 资助金额:
$ 33.26万 - 项目类别:
Grant-in-Aid for Early-Career Scientists














{{item.name}}会员




