真骨魚類の腎臓による塩分代謝の新たなメカニズムを発見ー魚類の海水・淡水順応機構の理解を前進ー

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2026-10-01 東京科学大学

東京科学大学・東京大学の研究チームは、海水魚トラフグの腎臓・腸において、カリウムチャネルKcnj15がNa⁺-K⁺-2Cl⁻共輸送体Nkcc2と連携し、NaClの吸収・再吸収を支える新たな仕組みを明らかにした。従来、Nkcc2の機能維持に必要なK⁺を管腔側へ戻す「K⁺リサイクルチャネル」は魚類では特定されていなかった。解析の結果、Kcnj15がNkcc2と同じ管腔側細胞膜に局在し、K⁺リサイクルを担う可能性が示された。また、低塩分環境では腎臓のKcnj15やNkcc2の発現・局在が変化し、Nccを中心とする別のNaCl再吸収機構へ切り替わることも判明した。本成果は、魚類の浸透圧調節だけでなく、電解質輸送機構の進化やヒトの塩分・水分バランスの理解にもつながる。

真骨魚類の腎臓による塩分代謝の新たなメカニズムを発見ー魚類の海水・淡水順応機構の理解を前進ー
図1. 海水魚の浸透圧調節におけるNkcc2の役割。A. 海水魚の浸透圧調節機構。B. ヒト腎臓の遠位直尿細管におけるNKCC2とKCNJ1によるNaCl再吸収機構。C. 本研究で見いだされたトラフグ集合管におけるKcnj15の新たな役割。

<関連情報>

Kcnj15は、Kcnj1とは異なり、トラフグ(Takifugu rubripes)の腎尿細管上皮細胞および腸管上皮細胞の頂端膜においてNkcc2と共局在する Kcnj15, but not Kcnj1, localizes with Nkcc2 in the apical membranes of renal tubular and intestinal epithelial cells of marine pufferfish, Takifugu rubripes

Yohei Sakamoto, Keiichiro Fujimori, Yutaka Suzuki, and Akira Kato
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology  Published:30 September 2026
DOI:https://doi.org/10.1152/ajpregu.00287.2023

Abstract

In mammals, Na+-K+-2Cl− cotransporter 2 (Nkcc2) is localized in the apical membrane of the renal tubule and contributes to salt reabsorption. Nkcc2 localizes with K+ channels, such as the potassium inwardly rectifying channel subfamily J member 1 (Kcnj1), which provide K+ to the luminal fluid. In marine teleosts, Nkcc2 is expressed in the kidneys and intestine; however, the K+ channels localizing with it remain ambiguous. Here, tissue distribution analysis revealed that the paralogs of kcnj1 were expressed in the gills and other organs but not in the kidneys and intestines of the marine pufferfish, Takifugu rubripes. In contrast, kcnj15 was highly expressed in the kidneys, intestine, gills, and urinary bladder of the pufferfish. Immunohistochemical analysis showed that Kcnj15 localizes to the apical region with Nkcc2 and to the basolateral region with Na+/K+-ATPase (Nka) in the renal tubules and intestinal epithelial cells of marine pufferfish. The expression of kcnj15, nkcc2, and Na+-Cl− cotransporter (ncc) in the kidney was significantly increased in brackish water (1 ppt salinity) compared with that in seawater (35 ppt). In brackish water, Kcnj15 was localized to the basolateral side with Nka in the renal tubules. In the urinary bladder, Kcnj15 was localized to the basolateral side along with Nka in Ncc-positive epithelial cells in both seawater and brackish water. These results suggest that Kcnj15 is involved in the salt (re)absorption systems of the urinary and digestive systems in pufferfish in a manner dependent on the expressing cells and habitat salinity.

生物工学一般
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