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Mechanisms of Protein Assembly and Transport in Hair Cells

毛细胞中蛋白质组装和运输的机制

基本信息

批准号：
10403895
负责人：
Christopher L Cunningham
金额：
$ 7.37万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-01 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10403895
关键词：
Actins Affect Apical Binding Binding Proteins Biochemical Brain CRISPR/Cas technology Ca(2+)-Transporting ATPase Catechol O-Methyltransferase Cell surface Cells Co-Immunoprecipitations Cochlea Communication Complement Complementary DNA Data Defect Disease Endoplasmic Reticulum Endosomes Epithelial Cells Epitopes Fluorescence Microscopy Foundations Gene Targeting Genes Goals Golgi Apparatus Hair Cells Health Homologous Gene Human Impairment Individual Integral Membrane Protein Ion Channel Ion Channel Gating Label Length Libraries Link Mechanics Mediating Methyltransferase Molecular Morphology Mus Mutant Strains Mice Mutation Mutation Analysis Organelles Pathway interactions Point Mutation Process Property Proteins Quality of life Resolution Role Route Sensory Set protein Signal Transduction Stimulus Structure Surface Synapses Tertiary Protein Structure Testing Tissues Transmission Electron Microscopy Validation Yeasts Zebrafish auditory processing base deafness experimental study hearing impairment insight loss of function mutation mechanotransduction molecular marker mutant polarized cell protein protein interaction protein transport sound therapeutic development tool trafficking yeast two hybrid system

项目摘要

Project Summary/Abstract The overall goal of the project is to define and characterize the organelles and specialized molecular machinery for protein assembly, processing and transport in hair cells, and the defects in this process that cause deafness. We propose here to investigate the mechanisms by which TOMT regulates transport of a subset of functionally important proteins in hair cells, and to begin to uncover TOMT-associated proteins that participate. Based on our preliminary data, we hypothesize that TOMT is an endoplasmic reticulum protein that is critical for assembly and transport of a specific set of transmembrane proteins in hair cells. To test our hypothesis, we will: i) use immunolocalization and immunogold transmission electron microscopy to precisely localize TOMT to hair-cell specific transport organelles; ii) identify and characterize important TOMT functional domains; and iii) look for interaction partners for TOMT that functionally cooperate in hair cell protein transport. Our preliminary data show the feasibility of our approach. We anticipate that our studies will elucidate new insights into the unique molecular machinery of hair cell protein transport that establishes distinctive functional specializations critical for auditory processing. Furthermore, a better understanding of protein transport mechanisms in hair cells has the potential to provide important context for protein transport deficits that are common in hearing loss.

项目总结/文摘