Translational Genomics Group, Incliva Health Research Institute, 46010 Valencia, Spain.
Interdisciplinary Research Structure for Biotechnology and Biomedicine (ERI BIOTECMED), University of Valencia, 46100 Valencia, Spain.
Dis Model Mech. 2020 Sep 21;13(9):dmm041509. doi: 10.1242/dmm.041509.
nephrocytes share functional, structural and molecular similarities with human podocytes. It is known that podocytes express the rabphilin 3A () complex, and its expression is altered in mouse and human proteinuric disease. Furthermore, we previously identified a polymorphism that suggested a role for RPH3A protein in the development of urinary albumin excretion. As endocytosis and vesicle trafficking are fundamental pathways for nephrocytes, the objective of this study was to assess the role of the orthologue in , (), in the structure and function of nephrocytes. We confirmed that is required for the correct function of the endocytic pathway in pericardial nephrocytes. Knockdown of reduced the expression of the and genes, which encode proteins that are involved in protein uptake and filtration. We also found that reduced expression resulted in a disappearance of the labyrinthine channel structure and a reduction in the number of endosomes, which ultimately leads to changes in the number and volume of nephrocytes. Finally, we demonstrated that the administration of retinoic acid to IR-Rph nephrocytes rescued some altered aspects, such as filtration and molecular uptake, as well as the maintenance of cell fate. According to our data, Rph is crucial for nephrocyte filtration and reabsorption, and it is required for the maintenance of the ultrastructure, integrity and differentiation of the nephrocyte.
足细胞与人类足细胞具有功能、结构和分子相似性。已知足细胞表达 rabphilin 3A () 复合物，其表达在小鼠和人类蛋白尿疾病中发生改变。此外，我们之前发现了一种多态性，表明 RPH3A 蛋白在尿白蛋白排泄的发展中起作用。由于内吞作用和囊泡运输是肾细胞的基本途径，因此本研究的目的是评估 在 (()) 中对肾细胞结构和功能的作用。我们证实 在心脏肾细胞的内吞途径的正确功能中是必需的。 的敲低降低了编码参与蛋白摄取和过滤的蛋白的 和 基因的表达。我们还发现， 表达的减少导致迷宫状通道结构的消失和内体数量的减少，最终导致肾细胞数量和体积的变化。最后，我们证明了视黄酸对 IR-Rph 肾细胞的给药可挽救一些改变的方面，如过滤和分子摄取，以及细胞命运的维持。根据我们的数据，Rph 对肾细胞的过滤和重吸收至关重要，并且需要维持肾细胞的超微结构、完整性和分化。
