CHLORIDE CHANNEL OF OSTEOCLAST RUFFLED BORDER

描述(改编自申请人的摘要)：适当的规定 破骨细胞介导的骨吸收是维持骨吸收的关键 健康的骨骼。了解破骨细胞的分子调控可能会 为常见严重骨骼疾病带来新的治疗方法，如 骨质疏松。破骨细胞通过产生酸性隔膜吸收骨 在骨头表面。破骨细胞酸运输的关键成分 机制是在破骨细胞皱褶中表达的氯离子通道 边界。申请者的长期目标一直是识别分子 了解褶皱的边界氯化物通道的基础，并了解这是如何 经络可能调节酸的转运和骨吸收。具体目标 本提案的主要目的是：(1)完全分子克隆 编码褶皱的膜氯通道的序列；(2)生物化学 刻画经络复合体的特征；(3)探索 氯离子通道和非受体酪氨酸激酶，src和；(4)定义 骨的存在调节蛋白表达的机制 氯离子通道。

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.