Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, 303 Pharmacy Building, Buffalo, NY, 14214, USA.
Department of Internal Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, 875 Ellicott St, Buffalo, NY, 14214, USA.
Biochem Biophys Res Commun. 2020 Aug 27;529(3):740-746. doi: 10.1016/j.bbrc.2020.05.166. Epub 2020 Jul 19.
Endocytosis by podocytes is gaining increased attention as a biologic means of removing large proteins such as serum albumin from the glomerular barrier. Some of this function has been attributed to the megalin/cubilin (Lrp2/Cubn) receptor complex and the albumin recycling protein FcRn (Fcgrt). However, whether other glomerular cells possess the potential to perform this same phenomenon or express these proteins remains uncharacterized. Mesangial cells are uniquely positioned in glomeruli and represent a cell type capable of performing several diverse functions. Here, the expression of megalin and FcRn in murine mesangial cells along with the megalin adaptor protein Dab-2 (Dab2) was shown for the first time. Cubilin mRNA expression was detected, but the absence of the cubilin partner amnionless (Amn) suggested that cubilin is minimally functional, if at all, in these cells. Mesangial cell endocytosis of albumin was characterized and shown to involve a receptor-mediated process. Albumin endocytosis was significantly impaired (p < 0.01) under inducible megalin knockdown conditions in stably transduced mesangial cells. The current work provides both the novel identification of megalin and FcRn in mesangial cells and the functional demonstration of megalin-mediated albumin endocytosis.
足细胞的内吞作用作为一种从肾小球屏障中去除大蛋白（如血清白蛋白）的生物学手段，越来越受到关注。其中部分功能归因于巨球蛋白/穹窿蛋白（Lrp2/Cubn）受体复合物和白蛋白再循环蛋白 FcRn（Fcgrt）。然而，其他肾小球细胞是否具有执行相同现象或表达这些蛋白质的潜力仍未被描述。系膜细胞在肾小球中具有独特的位置，是一种能够执行多种不同功能的细胞类型。在这里，首次展示了小鼠系膜细胞中巨球蛋白和 FcRn 的表达，以及巨球蛋白衔接蛋白 Dab-2（Dab2）。检测到穹窿蛋白 mRNA 的表达，但穹窿蛋白伴侣 Amnionless（Amn）的缺失表明，穹窿蛋白在这些细胞中功能有限，如果有的话。特征化了白蛋白在内皮细胞中的内吞作用，并表明这涉及一个受体介导的过程。在稳定转导的系膜细胞中，诱导巨球蛋白敲低条件下，白蛋白内吞作用显著受损（p<0.01）。目前的工作不仅首次鉴定了系膜细胞中的巨球蛋白和 FcRn，还证明了巨球蛋白介导的白蛋白内吞作用。
