School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan; Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan; Center for Biological Resources and Informatics, Tokyo Institute of Technology, Yokohama, Japan; Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
J Biol Chem. 2023 Jan;299(1):102740. doi: 10.1016/j.jbc.2022.102740. Epub 2022 Nov 23.
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 pH, 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) uniporter, B(OH)-OH cotransporter, or B(OH)/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.
硼酸是动物体内重要的微量营养素;然而,过量的硼酸对它们是有毒的。目前人们对动物体内硼酸的整体内稳态知之甚少。海水中(SW)含有 0.4mM 的硼酸,由于海洋鱼类饮用 SW,因此它们的泌尿系统被用作硼酸排泄系统的模型。我们发现,适应淡水和 SW 的海水养殖河豚(河鲀,Takifugu obscurus)的膀胱尿液分别含有 0.020 和 19mM 的硼酸(相差 950 倍),表明存在强大的硼酸排泄肾脏系统。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,河豚 Slc4a11 的直系同源物 Slc4a11A 的肾脏表达明显增加,Slc4a11A 定位于肾小管的顶膜。当将河豚 Slc4a11A 表达在非洲爪蟾卵母细胞中时,暴露于含有硼酸和电压钳的介质中会引发全细胞外向电流、pH 值显著增加和硼含量增加。此外,Slc4a11A 的活性不受细胞外 Na 的影响。这些结果表明,河豚 Slc4a11A 是一种电活性硼酸转运蛋白,作为 B(OH)同向转运体、B(OH)-OH 共转运体或 B(OH)/H 交换体发挥作用。这些观察结果表明,Slc4a11A 参与 SW 鱼类肾脏中硼酸的肾小管分泌,可能是由尿液的负膜电位和低 pH 值诱导的。