Lamp1 mediates lipid transport, but is dispensable for autophagy in Drosophila
Lamp1 mediates lipid transport, but is dispensable for autophagy in Drosophila
复制标题
Lamp1介导脂质转运，但在果蝇的自噬中是必不可少的
DOI：
10.1080/15548627.2022.2038999
复制
发表时间：
2022-03-11
期刊：
影响因子：
13.3
通讯作者：
Jenny, Andreas
中科院分区：
文献类型：
--
作者：
Chaudhry, Norin;Sica, Margaux;Jenny, Andreas
内溶酶体系统不仅是细胞分解代谢机制的一个组成部分，其处理和释放营养物质以合成生物材料，而且还充当信号中枢以感知和协调细胞的能量状态与生长和分化。溶酶体功能障碍对囊泡转运依赖的大分子降解产生不利影响，从而对人类健康造成严重问题。在哺乳动物细胞中，溶酶体相关膜蛋白LAMP1和LAMP2的丢失强烈影响自噬和胆固醇运输。在这里，我们表明，以前未表征的果蝇Lamp1是一个真正的直系同源的脊椎动物LAMP1和LAMP2。令人惊讶的是，与lamp1 lamp2双突变小鼠相反，果蝇Lamp1不需要生存能力或自噬，这表明苍蝇和脊椎动物LAMP蛋白获得不同的功能，或者自噬缺陷lamp1 lamp2突变体可能有间接原因。然而，Lamp1缺乏导致果蝇中酸性细胞器数量增加。此外，我们发现，Lamp1突变幼虫有缺陷的脂质代谢，因为它们显示出升高水平的甾醇和二酰基甘油（DAGs）。由于DAGs是昆虫血淋巴（血液）中用于运输的主要脂质种类，因此我们的研究结果表明Lamp 1在脂质运输中具有更广泛的功能。我们的研究结果使果蝇成为研究LAMP蛋白在脂质同化中的作用的理想模型，而不受其储存的混杂影响，也不干扰自噬过程。
The endolysosomal system not only is an integral part of the cellular catabolic machinery that processes and recycles nutrients for synthesis of biomaterials, but also acts as signaling hub to sense and coordinate the energy state of cells with growth and differentiation. Lysosomal dysfunction adversely influences vesicular transport-dependent macromolecular degradation and thus causes serious problems for human health. In mammalian cells, loss of the lysosome associated membrane proteins LAMP1 and LAMP2 strongly affects autophagy and cholesterol trafficking. Here we show that the previously uncharacterized Drosophila Lamp1 is a bona fide ortholog of vertebrate LAMP1 and LAMP2. Surprisingly and in contrast to lamp1 lamp2 double-mutant mice, Drosophila Lamp1 is not required for viability or autophagy, suggesting that fly and vertebrate LAMP proteins acquired distinct functions, or that autophagy defects in lamp1 lamp2 mutants may have indirect causes. However, Lamp1 deficiency results in an increase in the number of acidic organelles in flies. Furthermore, we find that Lamp1 mutant larvae have defects in lipid metabolism as they show elevated levels of sterols and diacylglycerols (DAGs). Because DAGs are the main lipid species used for transport through the hemolymph (blood) in insects, our results indicate broader functions of Lamp1 in lipid transport. Our findings make Drosophila an ideal model to study the role of LAMP proteins in lipid assimilation without the confounding effects of their storage and without interfering with autophagic processes.