The neonatal Fc receptor (FcRn) rescues albumin and IgG from degradation following endocytosis and thereby extends the half-life of these plasma proteins. However, the pathways for the uptake of these soluble FcRn ligands, and the recycling itinerary of the FcRn-ligand complexes, have not been identified in primary cells. Here, we have defined the recycling of human albumin and IgG in primary mouse macrophages selectively expressing the human FcRn. Albumin is internalised by macropinocytosis; in the absence of FcRn, internalised albumin is rapidly degraded, while in the presence of FcRn albumin colocalises to SNX5-positive membrane domains and is partitioned into tubules emanating from early macropinosomes for delivery in transport carriers to the plasma membrane. Soluble monomeric IgG was also internalised by macropinocytosis and rapidly recycled by the same pathway. In contrast, the fate of IgG bound to surface Fcγ receptors differed from monomeric IgG endocytosed by macropinocytosis. Overall, our findings identify a rapid recycling pathway for FcRn ligands from early macropinosomes to the cell surface of primary cells.

中文翻译：

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FcRn介导初级巨噬细胞中早期巨胞体内吞白蛋白和IgG的快速回收。

新生儿Fc受体（FcRn）可以使白蛋白和IgG免受内吞作用后的降解，从而延长了这些血浆蛋白的半衰期。但是，尚未在原代细胞中确定摄取这些可溶性FcRn配体的途径以及FcRn-配体复合物的循环路线。在这里，我们定义了选择性表达人FcRn的原代小鼠巨噬细胞中人白蛋白和IgG的再循环。白蛋白通过巨胞饮作用而被内在化；在不存在FcRn的情况下，内化白蛋白会迅速降解，而在FcRn白蛋白的存在下共定位到SNX5阳性膜结构域，并被分成从早期大颗粒体发出的小管，以转运载体的形式传递到质膜。可溶性单体IgG也通过巨胞饮作用而被内在化，并通过同一途径快速回收。相反，与表面Fcγ受体结合的IgG的命运不同于通过巨胞饮作用被内吞的单体IgG。总体而言，我们的发现确定了FcRn配体从早期大颗粒体到原代细胞表面的快速回收途径。