A functional endosomal pathway is necessary for lysosome biogenesis in Drosophila.
A functional endosomal pathway is necessary for lysosome biogenesis in Drosophila.
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DOI：
10.1186/s12860-016-0115-7
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发表时间：
2016-11-16
期刊：
影响因子：
--
通讯作者：
Taillebourg E
中科院分区：
文献类型：
--
作者：
Jacomin AC;Fauvarque MO;Taillebourg E
溶酶体是真核细胞中主要的分解代谢间隔，其生物发生需要生物合成途径和内体途径的整合。内吞作用和自噬作用是溶酶体降解途径的主要输入。膜蛋白的降解特别需要内吞作用，而细胞质成分的降解则需要自噬作用。我们先前发现，去泛素化酶UBPY/USP8对于果蝇溶酶体的生物发生和有效的自噬是必需的。由于UBPY/USP8在内体系统中的功能已被广泛描述，我们假设干扰内体途径本身可能会影响溶酶体的生物发生。在本研究中，我们通过在脂肪体细胞中表达dsRNAs或针对内体机械组件的显性负突变体：Shibire、Rab4、Rab5、Chmp1和Rab7，在不同成熟水平的内小体阻止了内体途径的进展。我们观察到，在体内不同阶段抑制内体转运与溶酶体生物发生的缺陷有关，从而导致自噬通量受阻。我们的结果表明，溶酶体的生物发生和体内有效的自噬都需要完整的内体系统。本文的在线版本(doi：10.1186/s12860-0160115-7)包含补充材料，授权用户可以使用。
Lysosomes are the major catabolic compartment within eukaryotic cells, and their biogenesis requires the integration of the biosynthetic and endosomal pathways. Endocytosis and autophagy are the primary inputs of the lysosomal degradation pathway. Endocytosis is specifically needed for the degradation of membrane proteins whereas autophagy is responsible for the degradation of cytoplasmic components. We previously identified the deubiquitinating enzyme UBPY/USP8 as being necessary for lysosomal biogenesis and productive autophagy in Drosophila. Because UBPY/USP8 has been widely described for its function in the endosomal system, we hypothesized that disrupting the endosomal pathway itself may affect the biogenesis of the lysosomes. In the present study, we blocked the progression of the endosomal pathway at different levels of maturation of the endosomes by expressing in fat body cells either dsRNAs or dominant negative mutants targeting components of the endosomal machinery: Shibire, Rab4, Rab5, Chmp1 and Rab7. We observed that inhibition of endosomal trafficking at different steps in vivo is systematically associated with defects in lysosome biogenesis, resulting in autophagy flux blockade. Our results show that the integrity of the endosomal system is required for lysosome biogenesis and productive autophagy in vivo. The online version of this article (doi:10.1186/s12860-016-0115-7) contains supplementary material, which is available to authorized users.
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