Segurado Alicia, Rodríguez-Carrillo Alba, Castellanos Bárbara, Hernández-Galilea Emiliano, Velasco Almudena, Lillo Concepción
Department of Cell Biology and Pathology, University of Salamanca, Salamanca, Spain.
Institute of Neurosciences of Castilla y León (INCyL), University of Salamanca, Salamanca, Spain.
Front Neuroanat. 2022 Sep 23;16:983151. doi: 10.3389/fnana.2022.983151. eCollection 2022.
Apicobasal polarity is a hallmark of retinal pigment epithelium cells and is required to perform their functions; however, the precise roles of the different proteins that execute polarity are still poorly understood. Here, we have studied the expression and location of Scribble, the core member of the polarity basal protein complex in epithelial-derived cells, in human and mouse RPE cells in both control and pathological conditions. We found that Scribble specifically localizes at the basolateral membrane of mouse and human RPE cells. In addition, we observed an increase in the expression of Scribble during human RPE development in culture, while it acquires a well-defined basolateral pattern as this process is completed. Finally, the expression and location of Scribble were analyzed in human RPE cells in experimental conditions that mimic the toxic environment suffered by these cells during AMD development and found an increase in Scribble expression in cells that develop a pathological phenotype, suggesting that the protein could be altered in cells under stress conditions, as occurs in AMD. Together, our results demonstrate, for the first time, that Scribble is expressed in both human and mouse RPE and is localized at the basolateral membrane in mature cells. Furthermore, Scribble shows impaired expression and location in RPE cells in pathological conditions, suggesting a possible role for this protein in the development of pathologies, such as AMD.
顶-基极性是视网膜色素上皮细胞的一个标志,是其执行功能所必需的;然而,执行极性的不同蛋白质的确切作用仍知之甚少。在这里,我们研究了上皮来源细胞中极性基底蛋白复合物的核心成员Scribble在对照和病理条件下的人类和小鼠视网膜色素上皮(RPE)细胞中的表达和定位。我们发现Scribble特异性定位于小鼠和人类RPE细胞的基底外侧膜。此外,我们观察到在培养的人类RPE发育过程中Scribble的表达增加,而在这个过程完成时它获得了明确的基底外侧模式。最后,在模拟这些细胞在年龄相关性黄斑变性(AMD)发展过程中所遭受的毒性环境的实验条件下,分析了人类RPE细胞中Scribble的表达和定位,发现在出现病理表型的细胞中Scribble表达增加,这表明该蛋白在应激条件下的细胞中可能会发生改变,就像在AMD中那样。总之,我们的结果首次证明,Scribble在人类和小鼠RPE中均有表达,并定位于成熟细胞的基底外侧膜。此外,Scribble在病理条件下的RPE细胞中表达和定位受损,提示该蛋白在诸如AMD等病理发展过程中可能发挥作用。