Division of Pathophysiology, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
Division of Pathophysiology, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
Biochim Biophys Acta Biomembr. 2021 Jul 1;1863(7):183617. doi: 10.1016/j.bbamem.2021.183617. Epub 2021 Mar 31.
The progress on mammalian superaquaporin (sAQP), AQP11 and AQP12, in the past seven years is brought up to date from the previous review. This subfamily is separated because of the very low homology with other AQP subfamilies and it is present only in multicellular organisms excluding fungi and plants. Its unique intracellular localization, specifically in the ER has made its functional studies challenging, but it may function as glyceroporin, aquaporin and peroxiporin, HO transporter. Knowledge on AQP11 has been expanded by tissue specific conditional knockout mice and by the identification of a SNP associated with kidney diseases. Moreover, the functional identification of AQP11 as a peroxiporin has expanded the role of AQP11 to the regulation of intracellular HO homeostasis to prevent ER stress, which awaits further in vivo studies. As kidney-specific AQP11 knockout of developed kidney has produced little phenotype, AQP11 is critical for kidney development but its physiological significance remains to be clarified. On the other hand, little has been known on pancreas-specific AQP12. To move this field forward, the results of sAQP in lower animals will be necessary to obtain the insights into the role of mammalian sAQP, which hopefully will lead to the discovery of therapeutic targets.
本文对上一个综述进行了更新,对过去七年中哺乳动物超大孔蛋白(sAQP)、AQP11 和 AQP12 的研究进展进行了总结。该亚家族与其他 AQP 亚家族的同源性非常低,只存在于多细胞生物中(真菌和植物除外),因此被分离出来。其独特的细胞内定位,特别是在内质网(ER),使得其功能研究具有挑战性,但它可能作为甘油通道蛋白、水通道蛋白和过氧化物通道蛋白、HO 转运体发挥作用。组织特异性条件性敲除小鼠和与肾脏疾病相关的 SNP 的鉴定,扩展了对 AQP11 的认识。此外,AQP11 作为过氧化物通道蛋白的功能鉴定,将 AQP11 的作用扩展到调节细胞内 HO 稳态以防止 ER 应激,这有待进一步的体内研究。由于发育中的肾脏特异性敲除 AQP11 的表型变化很小,AQP11 对肾脏发育至关重要,但它的生理意义仍有待阐明。另一方面,对胰腺特异性 AQP12 的了解甚少。为了推动这一领域的发展,需要获得低等动物 sAQP 的研究结果,以深入了解哺乳动物 sAQP 的作用,希望这将有助于发现治疗靶点。