Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Department of Biochemistry, Meiji Pharmaceutical University, Tokyo 204-8588, Japan.
J Cell Sci. 2017 Oct 15;130(20):3568-3577. doi: 10.1242/jcs.200519. Epub 2017 Aug 21.
The small GTPase Arl8b localizes primarily to lysosomes and is involved in lysosomal motility and fusion. Here, we show that Arl8b is required for lysosomal degradation of maternal proteins in the visceral yolk sac endoderm (VYSE), an apical cell layer of the visceral yolk sac, of mouse embryos. The VYSE actively takes up maternal materials from uterine fluid and degrades them in lysosomes to provide breakdown products to the embryo. Arl8b gene-trap mice ( ) displayed decreased early embryo body size. The VYSE exhibited defective endocytic trafficking to the lysosome and accumulation of maternal proteins such as albumin and immunoglobulin G in late endocytic organelles. Furthermore, mice in which Arl8b was ablated specifically in the VYSE also showed decreased embryo body size, defects in trafficking to the lysosome and reduction of the free amino acid level in the embryos. Taken together, these results suggest that Arl8b mediates lysosomal degradation of maternal proteins in the VYSE, thereby contributing to mouse embryonic development.
小分子 GTPase Arl8b 主要定位于溶酶体,并参与溶酶体的运动和融合。在这里,我们表明 Arl8b 是小鼠胚胎中内脏卵黄囊内胚层(VYSE)即内脏卵黄囊的顶端细胞层中母源蛋白溶酶体降解所必需的。VYSE 从子宫液中主动摄取母源物质,并在溶酶体中将其降解,为胚胎提供降解产物。Arl8b 基因捕获小鼠()显示出早期胚胎体型减小。VYSE 表现出向溶酶体的内吞运输缺陷,以及母源蛋白(如白蛋白和免疫球蛋白 G)在晚期内吞细胞器中的积累。此外,特异性在 VYSE 中剔除 Arl8b 的 小鼠也显示出胚胎体型减小、向溶酶体运输缺陷以及胚胎中游离氨基酸水平降低的现象。综上所述,这些结果表明 Arl8b 介导了 VYSE 中母源蛋白的溶酶体降解,从而有助于小鼠胚胎发育。