CHLORIDE CHANNEL OF OSTEOCLAST RUFFLED BORDER

破骨细胞氯离子通道褶皱边框

• 批准号: 6171372
• 负责人: JOHN C EDWARDS
• 金额: $ 17.83万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6171372
• 关键词: RNase protection assay; SDS polyacrylamide gel electrophoresis; autoradiography; biological transport; chloride channels; gel filtration chromatography; hydrochloric acid; immunoprecipitation; molecular cloning; nucleic acid sequence; osteoclasts; pathologic bone resorption; phosphorylation; physiologic bone resorption; polymerase chain reaction; protein tyrosine kinase; stainings; tissue /cell culture; western blottings

DESCRIPTION (Adapted from the Applicant's Abstract): Appropriate regulation of osteoclast-mediated bone resorption is essential for maintenance of healthy bone. Understanding the molecular regulation of osteoclasts may lead to new therapeutic approaches to common serious bone diseases like osteoporosis. Osteoclasts resorb bone by generating an acidic compartment on the bone surface. A key component of the osteoclast acid transport mechanism is a chloride channel which is expressed in the osteoclast-ruffled border. The applicant's long-term goals have been to identify the molecular basis of the ruffled border chloride channel and to understand how this channel may regulate acid transport and bone resorption. The Specific Aims of the present proposal are to: (1) complete molecular cloning of the sequences encoding the ruffled membrane chloride channel; (2) biochemically characterize the channel complex; (3) explore the relationship between the chloride channel and the non-receptor tyrosine kinases, src, and; (4) define the mechanism by which the presence of bone regulates expression of the chloride channel.

描述（改编自申请人摘要）：适当的法规 破骨细胞介导的骨吸收对于维持 健康的骨骼 了解破骨细胞的分子调控， 为常见的严重骨骼疾病带来新的治疗方法， 骨质疏松 破骨细胞通过产生酸性隔室来吸收骨 在骨头表面。 破骨细胞酸运输的关键成分 机制是一个氯离子通道，表达在破骨细胞-皱褶 边境 申请人的长期目标是鉴定 皱褶边缘氯离子通道的基础，并了解这是如何 通道可调节酸转运和骨吸收。 具体目标 本建议的主要内容是：（1）完成 编码皱褶膜氯离子通道的序列;（2）生物化学 （3）探讨了通道复合体与 氯离子通道和非受体酪氨酸激酶，src，和;（4）定义 骨的存在调节骨的表达的机制， 氯离子通道