Arl8b is required for lysosomal degradation of maternal proteins in the visceral yolk sac endoderm of mouse embryos
Arl8b is required for lysosomal degradation of maternal proteins in the visceral yolk sac endoderm of mouse embryos
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DOI：
10.1242/jcs.200519
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发表时间：
2017-10-15
影响因子：
4
通讯作者：
Kontani, Kenji
中科院分区：
文献类型：
--
作者：
Oka, Miho;Hashimoto, Keisuke;Kontani, Kenji
小的GTdR Arl 8b主要定位于溶酶体，并参与溶酶体运动和融合。在这里，我们表明，Arl 8b是必需的溶酶体降解母体蛋白质的内脏卵黄囊内胚层（VYSE），顶端细胞层的内脏卵黄囊，小鼠胚胎。VYSE主动从子宫液中吸收母体物质，并在溶酶体中降解它们，为胚胎提供分解产物。Ar 18 b基因诱捕小鼠（Ar 18 b（-/-））表现出早期胚胎体大小减小。Arl 8b（-/-）VYSE表现出有缺陷的向溶酶体的内吞运输和母体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，甲状腺素运载蛋白-Cre;其中Arl 8b在VYSE中被特异性消融的Arl 8b（flox/flox）小鼠也显示出胚胎体大小减小、向溶酶体运输的缺陷和胚胎中游离氨基酸水平的降低。总之，这些结果表明，Arl 8b介导VYSE中母体蛋白的溶酶体降解，从而有助于小鼠胚胎发育。
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 (Arl8b(-/-)) displayed decreased early embryo body size. The Arl8b(-/-) VYSE exhibited defective endocytic trafficking to the lysosome and accumulation of maternal proteins such as albumin and immunoglobulin G in late endocytic organelles. Furthermore, Transthyretin-Cre; Arl8b(flox/flox) 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.