期刊
BIOCHEMICAL JOURNAL
卷 377, 期 -, 页码 665-674出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20030956
关键词
antiporter; cystinuria; epithelial transport; heteromeric amino acid transporter; membrane transport; structure-function relationship
Apical reabsorption of dibasic amino acids and cystine in kidney is mediated by the heteromeric amino acid antiporter rBAT/b(0.+)AT (system b(0.+)). Mutations in rBAT cause cystinuria type A, whereas mutations in b(0.+)AT cause cystinuria type B.b(0.+)AT is the catalytic subunit, whereas it is believed that rBAT helps the routing of the rBAT/b(0.+)AT heterodimeric complex to the plasma membrane. In the present study, we have functionally characterized the cystinuria-specific R365W (Arg(365) --> Trp) mutation of human rBAT, which in addition to a trafficking defect, alters functional properties of the b(0.+) transporter. In oocytes, where human rBAT interacts with the endogenous b(0.+)AT subunit to form an active transporter, the rBAT(R365W) mutation caused a defect of arginine efflux without altering arginine influx or apparent affinities for intracellular or extracellular arginine. Transport of lysine or leucine remained unaffected. In HeLa cells, functional expression of rBAT(R365W)/b(0.+)AT was observed only at the permissive temperature of 33 degreesC. Under these conditions, the mutated transporter showed 50% reduction of arginine influx and a similar decreased accumulation of dibasic amino acids. Efflux of arginine through the rBAT(R365W)/b(0.+)AT holotransporter was completely abolished. This supports a two-translocation-pathway model for antiporter b(0.+), in which the efflux pathway in the rBAT(R365W)/b(0.+)AT holotransporter is defective for arginine translocation or dissociation. This is the first direct evidence that mutations in rBAT may modify transport properties of system b(0.+).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据