MOLECULAR PHYSIOLOGY OF RENAL K+/ CL- COTRANSPORTERS

描述（改编自申请人的摘要）：电中性KCl 在许多不同的细胞类型中已经描述了共转运蛋白， 在细胞体积调节和跨上皮氯化物中起重要作用 在许多肾单位段中运输。KCl共转运蛋白的研究是 受限于缺乏分子信息。第一次KCl 共转运蛋白被克隆。随后，首席研究员克隆了 两种全新的协同转运蛋白KCC3和KCC4。长期目标是 基金建议是阐明分子机制和生理作用 这些氯化钾协同转运蛋白的作用使用新完成的蛋白质序列， 首席研究员设计了一组特异性抗体目标是 用这些抗体来研究这三种蛋白的分布和调节， 肾脏KCC。对这些协同转运蛋白的功能研究将确定 细胞内氨基酸决定KCC 3和KCC 4的体积敏感性， 所述跨膜氨基酸决定阳离子亲和力。

DESCRIPTION (Adapted from the Applicant's Abstract): Electro-neutral KCl co-transporters have been described in a number of different cell types and play important roles in cell volume regulation and in trans-epithelial chloride transport in many nephron segments. The study of KCl co-transporters was limited by a lack of molecular information. Recently the first KCl co-transporter was cloned. Subsequently the principal investigator has cloned two completely new co-transporters KCC3 and KCC4. The long-term goals of this grant proposal are to clarify the molecular mechanisms and physiological role of these KCl co-transporters. Using the newly completed protein sequences the principal investigator has designed a panel of specific antibodies. The goal is to use these antibodies to study the distribution and regulation of the three renal KCCs. Functional studies of these co-transporters will determine which intracellular amino acids determine the volume sensitivity of KCC3 and KCC4 and which transmembrane amino acids determine cation affinity.