Dynamic interaction among proteins in hair cells
毛细胞中蛋白质之间的动态相互作用
基本信息
- 批准号:9527906
- 负责人:
- 金额:$ 49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-03-01 至 2019-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcousticsAdhesivesAffectAgeAllelesAnatomyAuditoryAuditory PhysiologyBehaviorBindingBinding ProteinsBiochemistryBiologicalBiophysicsCDH23 geneCRISPR/Cas technologyCalmodulinCell ShapeCellsCellular MorphologyCellular StructuresCellular biologyCentrosomeCochleaCodeComplexCytoplasmic ProteinDataDevelopmentDimensionsElectrophysiology (science)Epithelial CellsExcisionFoundationsFutureGFI1 geneGene MutationGenesGenomicsGoalsHair CellsHearingHumanImmunohistochemistryImpairmentIn VitroIndividualInheritedKnock-in MouseKnock-outKnockout MiceKnowledgeLabyrinthLacZ GenesLinkMaintenanceMapsMass Spectrum AnalysisMediatingMethodsMicrotubule-Associated ProteinsMicrotubulesMinus End of the MicrotubuleMolecularMolecular BiologyMorphogenesisMusMutationNamesNeuraxisNeuronsOrganOrgan of CortiOuter Hair CellsPathologyPathway interactionsPatientsPatternPeripheralPharmacological TreatmentPhysiologicalPhysiologyPigmentation physiologic functionPillar CellPlayProtein IsoformsProteinsProteomicsReflex actionRegulationReporterReporter GenesRoleSensory DisordersSignal TransductionSpectrinSteelStructureSupporting CellSystemTestingTherapeuticTransport VesiclesUsher SyndromeVesicle Transport PathwayWD RepeatWaardenburg syndromecell typedeafnessdesignexperimental studyexternal ear auriclegene therapyhearing impairmentin vitro Assayin vivomouse modelmutantmutant mouse modelnegative affectnoveloperationpolarized cellpreventsoundspiral ganglion
项目摘要
PROJECT SUMMARY
The cochlea converts sound waves into electrical signals to convey information to the central nervous
system. Highly specialized cells including hair cells, supporting cells and spiral ganglion neurons mediate this
operation. Because complex and sophisticated microtubule (MT) networks are needed for the individualized
cell shapes and structures required for peripheral signal coding, uncovering the protein networks that modulate
MT organization will enrich our understanding of both normal and impaired cochlear physiology. The goal of
this proposal is to investigate three largely unexplored proteins, whose functions may be important for the
regulation of MTs in the inner ear: CAMSAP3, CDH23-C, and WDR47. CAMSAP3 is a MT minus-end binding
protein, while CDH23-C, a cytoplasmic isoform of CDH23, and WDR47, a protein of unknown function, both
interact with CAMSAP3. Deletion or mutation of these genes is linked to hearing impairment in humans and in
mouse models. Thus, they may potentially be responsible for causing hereditary hearing loss. In AIM I, we
investigate the role of CAMSAP3 using conditional knockout mouse models that lack CAMSAP3 in individual
cell types in the cochlea including hair cells, supporting cells, and spiral ganglion neurons. We will examine
these mice using various anatomical and physiological methods to determine the function of CAMSAP3 in
hearing. In AIM II, we investigate the functional consequences of impaired interaction between CDH23-C and
CAMSAP3. We will generate a CDH23-C mutant mouse model that mimics the human Usher Syndrome 1D
mutation that negatively affects this interaction, and evaluate the importance of the role of CDH23-C in MT
regulation via its interaction with CAMSAP3. The experiments are designed to reveal a novel molecular
mechanism that involves MT modulation in the cochlea and that is implicated in Usher Syndrome 1D. In Aim
III, we investigate the function of WDR47 in hearing through both in vivo and in vitro approaches. We will
determine the detailed expression patterns of WDR47 in the cochlea and investigate WDR47's contribution to
hearing using WDR47 knockout mice. We will also dissect the molecular basis of interactions between WDR47
and CAMSAP3, and uncover WDR47-associated proteins through both biochemistry and proteomics. Taken
together, the proposed studies aim to provide critical information regarding the protein networks that regulate
MT organization in the cochlea by focusing on three proteins. Our comprehensive approach utilizes a variety of
methods including molecular and cell biology, biophysics, electrophysiology, in vivo physiology and mass
spectrometry, thereby allowing us to achieve our goals. The data obtained from the proposed experiments will
provide new knowledge about the molecular mechanisms underlying the pathology of hearing loss, and enrich
our understanding of the protein networks important for hearing and deafness. This information will guide our
current and future efforts in directing treatments and/or in preventing hearing loss.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Jing Zheng', 18)}}的其他基金
DYNAMIC INTERATION AMONG PROTEINS IN HAIR CELLS
毛细胞中蛋白质之间的动态相互作用
- 批准号:
8297956 - 财政年份:2012
- 资助金额:
$ 49万 - 项目类别:
DYNAMIC INTERATION AMONG PROTEINS IN HAIR CELLS
毛细胞中蛋白质之间的动态相互作用
- 批准号:
8620644 - 财政年份:2012
- 资助金额:
$ 49万 - 项目类别:
DYNAMIC INTERATION AMONG PROTEINS IN HAIR CELLS
毛细胞中蛋白质之间的动态相互作用
- 批准号:
8431347 - 财政年份:2012
- 资助金额:
$ 49万 - 项目类别:
DYNAMIC INTERATION AMONG PROTEINS IN HAIR CELLS
毛细胞中蛋白质之间的动态相互作用
- 批准号:
9022461 - 财政年份:2012
- 资助金额:
$ 49万 - 项目类别:
Preventing hair cell loss by regulating prestin's function
通过调节 prestin 的功能来防止毛细胞损失
- 批准号:
7933797 - 财政年份:2009
- 资助金额:
$ 49万 - 项目类别:
Preventing hair cell loss by regulating prestin's function
通过调节 prestin 的功能来防止毛细胞损失
- 批准号:
7827241 - 财政年份:2009
- 资助金额:
$ 49万 - 项目类别:
Investigating the nature of prestin-associated proteins
研究 prestin 相关蛋白的性质
- 批准号:
7211417 - 财政年份:2005
- 资助金额:
$ 49万 - 项目类别:
Investigating the nature of prestin-associated proteins
研究 prestin 相关蛋白的性质
- 批准号:
7020704 - 财政年份:2005
- 资助金额:
$ 49万 - 项目类别:
Investigating the nature of prestin-associated proteins
研究 prestin 相关蛋白的性质
- 批准号:
6923414 - 财政年份:2005
- 资助金额:
$ 49万 - 项目类别:
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