Wide expression of type I Na+-phosphate cotransporter 3 (NPT3/SLC17A2), a membrane potential-driven organic anion transporter
Wide expression of type I Na+-phosphate cotransporter 3 (NPT3/SLC17A2), a membrane potential-driven organic anion transporter
复制标题
DOI：
10.1152/ajpcell.00048.2015
复制
发表时间：
2015-07-15
影响因子：
5.5
通讯作者：
Moriyama, Yoshinori
中科院分区：
文献类型：
--
作者：
Togawa, Natsuko;Juge, Narinobu;Moriyama, Yoshinori
膜电位（Delta psi）驱动和依赖Cl的有机阴离子运输是溶质载体家族17 （SLC17）转运体家族的主要功能。虽然主要成员的转运底物和生理相关性已经很清楚，但已知的Na+-phosphate cotransporter 3 （NPT3）的SLC17A2蛋白的特征还远远不够。在本研究中，我们研究了小鼠SLC17A2蛋白（mNPT3）的转运特性和表达模式。含有纯化的mNPT3蛋白的蛋白脂质体以δ psi和Cl依赖的方式吸收放射性标记的对氨基马嘌呤（PAH）。SLC17家族成员的常见抑制剂4,4'-二异硫氰基二苯乙烯- 2,2'-二磺酸（DIDs）和Evans蓝可抑制mnpt3介导的PAH摄取。各种阴离子化合物，如亲水性非甾体抗炎药（NSAIDs）和尿酸盐，也能抑制多环芳烃的摄取。与这些观察结果一致，蛋白脂质体以δ psi和Cl依赖的方式吸收放射性标记的尿酸盐。利用mNPT3特异性抗体结合RT-PCR免疫组化发现，mNPT3存在于多种组织中，包括肝胆管、肾尿小管管腔膜、胎盘母侧合胞滋养细胞、甲状腺滤泡细胞顶膜、肺细支气管上皮细胞、大脑血管周围星形胶质细胞等。这些结果表明mNPT3是一种多特异性有机阴离子转运体，参与尿酸盐在全身的循环。
Membrane potential (Delta psi)-driven and Cl--dependent organic anion transport is a primary function of the solute carrier family 17 (SLC17) transporter family. Although the transport substrates and physiological relevance of the major members are well understood, SLC17A2 protein known to be Na+-phosphate cotransporter 3 (NPT3) is far less well characterized. In the present study, we investigated the transport properties and expression patterns of mouse SLC17A2 protein (mNPT3). Proteoliposomes containing the purified mNPT3 protein took up radiolabeled p-aminohippuric acid (PAH) in a Delta psi- and Cl--dependent manner. The mNPT3-mediated PAH uptake was inhibited by 4,4'-diisothiocyanostilbene- 2,2'-disulfonic acid (DIDs) and Evans blue, common inhibitors of SLC17 family members. The PAH uptake was also inhibited by various anionic compounds, such as hydrophilic nonsteroidal anti-inflammatory drugs (NSAIDs) and urate. Consistent with these observations, the proteoliposome took up radiolabeled urate in a Delta psi- and Cl--dependent manner. Immunohistochemistry with specific antibodies against mNPT3 combined with RT-PCR revealed that mNPT3 is present in various tissues, including the hepatic bile duct, luminal membranes of the renal urinary tubules, maternal side of syncytiotrophoblast in the placenta, apical membrane of follicle cells in the thyroid, bronchiole epithelial cells in the lungs, and astrocytes around blood vessels in the cerebrum. These results suggested that mNPT3 is a polyspecific organic anion transporter that is involved in circulation of urate throughout the body.