Seawater fish use an electrogenic boric acid transporter, Slc4a11A, for boric acid excretion by the kidney.
Seawater fish use an electrogenic boric acid transporter, Slc4a11A, for boric acid excretion by the kidney.
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DOI：
10.1016/j.jbc.2022.102740
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发表时间：
2023-01
影响因子：
4.8
通讯作者：
Romero, Michael F.
中科院分区：
文献类型：
--
作者：
Kato, Akira;Kimura, Yuuri;Kurita, Yukihiro;Chang, Min-Hwang;Kasai, Koji;Fujiwara, Toru;Hirata, Taku;Doi, Hiroyuki;Hirose, Shigehisa;Romero, Michael F.
硼酸是动物体内重要的微量营养素；然而，过量对它们来说是有毒的。人们对动物全身硼酸稳态知之甚少。海水 (SW) 含有 0.4 mM 硼酸，由于海水鱼类饮用海水，因此此处使用它们的泌尿系统作为硼酸排泄系统的模型。我们确定，适应淡水和 SW 的广盐河豚（河豚、暗纹东方鲀）的膀胱尿液中分别含有 0.020 和 19 mM 硼酸（相差 950 倍），表明存在强大的硼酸排泄肾系统。 Slc4a11 是植物硼转运蛋白 BOR1 的潜在动物同源物；然而，哺乳动物 Slc4a11 介导 H+ (OH−) 电导，但不转运硼酸。我们发现，从淡水转移到SW后，Slc4a11的河豚旁系同源物Slc4a11A的肾脏表达被显着诱导，并且Slc4a11A定位于肾小管的顶膜。当河豚 Slc4a11A 在非洲爪蟾卵母细胞中表达时，暴露于含有硼酸的培养基和电压钳会引发全细胞外向电流、pHi 显着增加和硼含量增加。此外，Slc4a11A 的活性不依赖于细胞外 Na+。这些结果表明河豚 Slc4a11A 是一种产电硼酸转运蛋白，可充当 B(OH)4− 单转运蛋白、B(OH)3-OH− 协同转运蛋白或 B(OH)3/H+ 交换蛋白。这些观察结果表明，Slc4a11A 参与了西南鱼肾小管硼酸的分泌，可能是由负膜电位和尿液低 pH 值诱导的。
Boric acid is a vital micronutrient in animals; however, excess amounts are toxic to them. Little is known about whole-body boric acid homeostasis in animals. Seawater (SW) contains 0.4 mM boric acid, and since marine fish drink SW, their urinary system was used here as a model of the boric acid excretion system. We determined that the bladder urine of a euryhaline pufferfish (river pufferfish, Takifugu obscurus) acclimated to fresh water and SW contained 0.020 and 19 mM of boric acid, respectively (a 950-fold difference), indicating the presence of a powerful excretory renal system for boric acid. Slc4a11 is a potential animal homolog of the plant boron transporter BOR1; however, mammalian Slc4a11 mediates H+ (OH−) conductance but does not transport boric acid. We found that renal expression of the pufferfish paralog of Slc4a11, Slc4a11A, was markedly induced after transfer from fresh water to SW, and Slc4a11A was localized to the apical membrane of kidney tubules. When pufferfish Slc4a11A was expressed in Xenopus oocytes, exposure to media containing boric acid and a voltage clamp elicited whole-cell outward currents, a marked increase in pHi, and increased boron content. In addition, the activity of Slc4a11A was independent of extracellular Na+. These results indicate that pufferfish Slc4a11A is an electrogenic boric acid transporter that functions as a B(OH)4− uniporter, B(OH)3-OH− cotransporter, or B(OH)3/H+ exchanger. These observations suggest that Slc4a11A is involved in the kidney tubular secretion of boric acid in SW fish, probably induced by the negative membrane potential and low pH of urine.
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