School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Biol Open. 2022 Jun 15;11(6). doi: 10.1242/bio.059150. Epub 2022 Jun 23.
Endocytosis mediates the cellular uptake of numerous molecules from the extracellular space and is a fundamentally important process. In the renal proximal tubule, the scavenger receptor megalin and its co-receptor cubilin mediate endocytosis of low molecular weight proteins from the renal filtrate. However, the extent to which megalin endocytosis relies on different components of the trafficking machinery remains relatively poorly defined in vivo. In this study, we identify a functional requirement for the F-BAR protein pacsin2 in endocytosis in the renal proximal tubule of zebrafish larvae. Pacsin2 is expressed throughout development and in all zebrafish tissues, similar to the mammalian orthologue. Within renal tubular epithelial cells, pacsin2 is enriched at the apical pole where it is localised to endocytic structures. Loss of pacsin2 results in reduced endocytosis within the proximal tubule, which is accompanied by a reduction in the abundance of megalin and endocytic organelles. Our results indicate that pacsin2 is required for efficient endocytosis in the proximal tubule, where it likely cooperates with other trafficking machinery to maintain endocytic uptake and recycling of megalin.
内吞作用介导细胞从细胞外空间摄取许多分子，是一个基本重要的过程。在肾近端小管中，清道夫受体 megalin 和其辅助受体 cubilin 介导从肾滤过液中摄取低分子量蛋白质。然而，megalin 内吞作用在多大程度上依赖于运输机制的不同成分，在体内仍然相对定义不明确。在这项研究中，我们确定了 F-BAR 蛋白 pacsin2 在斑马鱼幼虫肾近端小管内吞作用中的功能需求。Pacsin2 在整个发育过程中和所有斑马鱼组织中表达，类似于哺乳动物同源物。在肾小管上皮细胞中，pacsin2 在顶端极富集，位于内吞结构处。pacsin2 的缺失导致近端小管内吞作用减少，同时 megalin 和内吞细胞器的丰度减少。我们的结果表明，pacsin2 是近端小管中高效内吞作用所必需的，它可能与其他运输机制合作，维持 megalin 的内吞摄取和再循环。
