MUTANT CFTR TRAFFICKING

变种 CFTR 贩运

• 批准号: 7358049
• 负责人: STEVE KELLER
• 金额: $ 0.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7358049
• 关键词: MUTANT; CFTR; TRAFFICKING

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cystic fibrosis is one of the most common inherited disorders, afflicting approximately 1 in 3000 newborn. The primary cause of cystic fibrosis is a phenylalanine deletion in the CFTR chloride channel at position 508, which is designated deltaF508 CFTR: individuals homozygous for this mutation develop severe lung inflammation and typically have a shortened life-span. DeltaF508 CFTR is trafficking deficient; it fails to reach the cell surface, and appears to accumulate in intracellular compartments where it undergoes degradation or forms aggregates. The mechanistic basis for the trafficking deficiency is largely unknown. We would like to trace the progression of wild type and mutant CFTR in the secretory pathway using cells that are deficient in components of the cellular quality control machinery. Methods to express CFTR in cells deficient in ubiquitinylation, COP I complex formation and cellular sorting are available to examine the pathway of trafficking. The Flash technique may provide a useful tool to trace CFTR in these cells to elucidate the mechanistic basis of the trafficking deficiency.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。囊性纤维化是最常见的遗传性疾病之一，大约每 3000 名新生儿中就有 1 人患有囊性纤维化。 囊性纤维化的主要原因是 CFTR 氯化物通道 508 位的苯丙氨酸缺失，被称为 deltaF508 CFTR：这种突变纯合的个体会出现严重的肺部炎症，并且通常寿命缩短。 DeltaF508 CFTR 流量不足；它无法到达细胞表面，并且似乎积聚在细胞内区室中，并在那里经历降解或形成聚集体。贩运缺陷的机制基础在很大程度上尚不清楚。我们希望使用缺乏细胞质量控制机制的细胞来追踪野生型和突变型 CFTR 在分泌途径中的进展。在泛素化、COP I 复合物形成和细胞分选缺陷的细胞中表达 CFTR 的方法可用于检查运输途径。 Flash 技术可能提供有用的工具来追踪这些细胞中的 CFTR，以阐明贩运缺陷的机制基础。