The fatty acyl-CoA reductase Waterproof mediates airway clearance in Drosophila
The fatty acyl-CoA reductase Waterproof mediates airway clearance in Drosophila
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DOI：
10.1016/j.ydbio.2013.10.022
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发表时间：
2014-01-01
影响因子：
2.7
通讯作者：
Schuh, Reinhard
中科院分区：
文献类型：
--
作者：
Jaspers, Martin H. J.;Pflanz, Ralf;Schuh, Reinhard
从液体到充满气体的管状网络的转变是脊椎动物肺和无脊椎动物气管系统正常功能的先决条件。然而，气体填充过程的机制仍然不清楚。在这里，我们表明，防水编码脂肪酰辅酶A还原酶（FAR），是必不可少的气体填充的气管在果蝇胚胎发育过程中，并不影响分支网络的形成或关键的气管成熟过程。然而，电子显微镜分析表明，在防水突变体胚胎的形成最外层的气管角质层亚层，信封，被破坏和疏水性气管涂层被损坏。遗传和功能获得实验表明，对于气管气体填充过程的开始，非细胞自主防水功能。有趣的是，Waterproof将24和26个碳原子的长链脂肪酸还原为脂肪醇。因此，我们提出，防水在气管气体填充中起着关键作用，通过提供非常长链的脂肪醇，作为潜在的底物蜡酯合成或相关的疏水物质，最终涂层的气管内衬。疏水性又降低了气管内液体的拉伸强度，导致气泡的形成，气泡是随后气体填充的焦点。防水代表了迄今为止描述的第一种酶，其对于气管气体填充是必需的，而不影响分支形态。考虑到其在整个进化过程中的保守性，防水直系同源物可能在脊椎动物肺中发挥类似的作用。(C)2013 Elsevier Inc. All rights reserved.
The transition from a liquid to a gas filled tubular network is the prerequisite for normal function of vertebrate lungs and invertebrate tracheal systems. However, the mechanisms underlying the process of gas filling remain obscure. Here we show that waterproof encoding a fatty acyl-CoA reductase (FAR), is essential for the gas filling of the tracheal tubes during Drosophila embryogenesis, and does not affect branch network formation or key tracheal maturation processes. However, electron microscopic analysis reveals that in waterproof mutant embryos the formation of the outermost tracheal cuticle sublayer, the envelope, is disrupted and the hydrophobic tracheal coating is damaged. Genetic and gain-of-function experiments indicate a non-cell-autonomous waterproof function for the beginning of the tracheal gas filling process. Interestingly, Waterproof reduces very long chain fatty acids of 24 and 26 carbon atoms to fatty alcohols. Thus, we propose that Waterproof plays a key role in tracheal gas filling by providing very long chain fatty alcohols that serve as potential substrates for wax ester synthesis or related hydrophobic substances that ultimately coat the inner lining of the trachea. The hydrophobicity in turn reduces the tensile strength of the liquid inside the trachea, leading to the formation of a gas bubble, the focal point for subsequent gas filling. Waterproof represents the first enzyme described to date that is necessary for tracheal gas filling without affecting branch morphology. Considering its conservation throughout evolution, Waterproof orthologues may play a similar role in the vertebrate lung. (C) 2013 Elsevier Inc. All rights reserved.