Understanding the mechanism and role of cell membrane repair in Miyoshi Myopathy

了解细胞膜修复在三好肌病中的机制和作用

• 批准号: 8269083
• 负责人: JYOTI K JAISWAL
• 金额: $ 32.37万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-02 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8269083
• 关键词: ANXA2 gene; Affect; Annexin A1; Attention; Binding; Biochemical; Biological; Calcium; Candidate Disease Gene; Cell membrane; Cell surface; Cells; Cleaved cell; Clinical; DYSF gene; Defect; Diagnosis; Disease; Endocytosis; Endosomes; Exocytosis; Family; Fibroblasts; Figs - dietary; Golgi Apparatus; Healed; Health; Knowledge; Label; Laboratories; Lead; Life; Limb-Girdle Muscular Dystrophies; Lysosomes; Mediating; Membrane; Molecular; Mus; Muscle; Muscle Cells; Muscular Dystrophies; Mutation; Myoblasts; Myopathy; Patients; Pharmaceutical Preparations; Play; Proteins; Proteome; Proteomics; Rest; Role; Sarcolemma; Site; Small Interfering RNA; Symptoms; Testing; Time; Toxin; Vesicle; Work; Wound Healing; base; cellular imaging; comparative; healing; improved; prevent; repaired; response; trafficking; wound

DESCRIPTION (provided by applicant): Muscular dystrophy is commonly caused by mutation in proteins that lead to sarcolemmal instability. However, work from several laboratories indicates that Miyoshi myopathy (MM) and limb girdle muscular dystrophy (LGMD) 2B, caused by defects in dysferlin expression is associated with poor healing of wounded sarcolemma. Poor healing of wounded muscles is believed to be due to poor calcium-triggered vesicle exocytosis. We have recently identified that non-dysferlin MM patient's are also poor at healing cellular wounds. Exocytosis of several different vesicles is affected by lack of dysferlin, while exocytosis of none of these vesicles appears to be deficient in non-dysferlin MM cells. Thus, it is not clear which of these (if any) vesicles are responsible for the poor healing of dysferlin deficient cells. This proposal utilizes proteomic and cell biological analysis to identify - 1) the vesicles responsible for poor healing of dysferlin-dependent and independent MM cells and 2) the molecules that regulate exocytosis of these vesicles. PUBLIC HEALTH RELEVANCE. The proposed work aims to identify cellular and molecular defect responsible for a type of muscular dystrophy associated with the inability of wounded muscle cells to heal. This work would aid in prediction, diagnosis and therapy of muscular dystrophies caused by poor healing of wounded cells.

描述（由申请人提供）：肌肉营养不良通常是由导致肌畸形不稳定性的蛋白质突变引起的。但是，来自几个实验室的工作表明，由Dysferlin表达缺陷引起的Miyoshi肌病（MM）和肢体腰围肌肉营养不良（LGMD）2B与受伤的肉骨运动的愈合不良有关。据信受伤的肌肉治愈不良是由于钙触发的囊泡胞吐作用不良。我们最近确定，非dysferlin MM患者在愈合细胞伤口方面也很差。几种不同囊泡的胞吐作用受dysferlin缺乏的影响，而这些囊泡的胞吐作用似乎都不缺乏dysferlin MM细胞。因此，尚不清楚这些（如果有）囊泡中的哪一个是dysferlin缺乏细胞的愈合不良的原因。该建议利用蛋白质组学和细胞生物学分析来识别-1）促成dysferlin依赖性和独立的MM细胞愈合不良的囊泡以及2）调节这些囊泡胞吐作用的分子。公共卫生相关性。提出的工作旨在识别导致与受伤的肌肉细胞无能为力有关的肌肉营养不良的一种细胞和分子缺陷。这项工作将有助于预测，诊断和治疗受伤细胞治愈不良引起的肌肉营养不良。