AQP1 Is Not Only a Water Channel: It Contributes to Cell Migration through Lin7/Beta-Catenin

BackgroundAQP1 belongs to aquaporins family, water-specific, membrane-channel proteins expressed in diverse tissues. Recent papers showed that during angiogenesis, AQP1 is expressed preferentially by microvessels, favoring angiogenesis via the increase of permeability In particular, in AQP1 null mice, endothelial cell migration is impaired without altering their proliferation or adhesion. Therefore, AQP1 has been proposed as a novel promoter of tumor angiogenesis. Methods/FindingsUsing targeted silencing of AQP1 gene expression, an impairment in the organization of F-actin and a reduced migration capacity was demonstrated in human endothelial and melanoma cell lines. Interestingly, we showed, for the first time, that AQP1 co-immunoprecipitated with Lin-7. Lin7-GFP experiments confirmed co-immunoprecipitation. In addition, the knock down of AQP1 decreased the level of expression of Lin-7 and β-catenin and the inhibition of proteasome contrasted partially such a decrease. Conclusions/SignificanceAll together, our findings show that AQP1 plays a role inside the cells through Lin-7/β-catenin interaction. Such a role of AQP1 is the same in human melanoma and endothelial cells, suggesting that AQP1 plays a global physiological role. A model is presented.背景： AQP1属于水通道蛋白（aquaporins）家族，是一类特异性介导水转运的膜通道蛋白，广泛表达于多种组织中。近期研究显示，在血管生成过程中，AQP1优先由微血管表达，通过提升血管通透性促进血管生成。尤为关键的是，在AQP1基因敲除小鼠体内，内皮细胞的迁移能力受损，但细胞增殖与黏附功能并未受到影响。因此，AQP1被提出为肿瘤血管生成的新型促进因子。 方法与研究结果： 通过靶向沉默AQP1基因的表达，研究团队在人内皮细胞与黑色素瘤细胞系中证实，F-肌动蛋白（F-actin）的细胞组装出现异常，且细胞迁移能力显著下降。值得注意的是，本研究首次发现AQP1可与Lin-7发生免疫共沉淀（co-immunoprecipitation），Lin7-GFP实验进一步验证了这一蛋白相互作用。此外，敲低AQP1的表达会降低Lin-7与β-连环蛋白（β-catenin）的蛋白表达水平，而蛋白酶体（proteasome）抑制剂可部分逆转该下调效应。 结论与意义： 综上，本研究结果表明，AQP1可通过与Lin-7/β-连环蛋白的相互作用在细胞内发挥调控功能。该调控机制在人黑色素瘤细胞与内皮细胞中保持一致，提示AQP1具备广泛的生理调控作用。本研究同时提出了对应的作用模型。