Genetic Studies of Spectrin in the Larval Fat Body of Drosophila melanogaster: Evidence for a Novel Lipid Uptake Apparatus
Genetic Studies of Spectrin in the Larval Fat Body of Drosophila melanogaster: Evidence for a Novel Lipid Uptake Apparatus
复制标题
DOI：
10.1534/genetics.113.155192
复制
发表时间：
2013-11-01
期刊：
影响因子：
3.3
通讯作者：
Dubreuil, Ronald R.
中科院分区：
文献类型：
--
作者：
Diaconeasa, Bianca;Mazock, G. Harper;Dubreuil, Ronald R.
Spectrin细胞骨架缺陷产生影响质膜、细胞极性和分泌膜运输的许多表型。然而，许多潜在的分子机制仍然无法解释流行的模型。在这里，我们使用的果蝇幼虫脂肪体作为遗传模型系统，以进一步阐明-血影蛋白功能的机制。这些结果为血影蛋白的功能以及膳食脂肪摄取和储存机制提供了意想不到的新见解。我们发现，损失的-或-血影蛋白的脂肪体消除了人口的小皮质脂滴和改变质膜结构，但不影响生物体的生存能力。我们提出了一种新的模型，其中-血影蛋白直接耦合在质膜脂滴在细胞质中的生长的脂质摄取。相反，-血影蛋白的强烈过度表达引起脂肪体萎缩和幼虫致死。- 血影蛋白的过度表达还扰乱了膳食脂肪从中肠到脂肪体的运输。这种超形态表型似乎是阻止脂肪细胞分泌脂质载体脂转运蛋白的结果。然而，这种中肠表型在血影蛋白功能丧失的情况下从未见过，这表明血影蛋白通常不是载脂蛋白分泌或功能所需的。- 血影蛋白的共过表达可以改善-血影蛋白的超形态表型。基于这里的过表达结果，我们建议-血影蛋白家族成员可能容易hypermorphic影响（包括分泌的影响），如果他们的活动没有得到适当的调节。
Spectrin cytoskeleton defects produce a host of phenotypes affecting the plasma membrane, cell polarity, and secretory membrane traffic. However, many of the underlying molecular mechanisms remain unexplained by prevailing models. Here we used the larval fat body of Drosophila melanogaster as a genetic model system to further elucidate mechanisms of -spectrin function. The results provide unexpected new insights into spectrin function as well as mechanisms of dietary fat uptake and storage. We show that loss of - or -spectrin in the fat body eliminated a population of small cortical lipid droplets and altered plasma membrane architecture, but did not affect viability of the organism. We present a novel model in which -spectrin directly couples lipid uptake at the plasma membrane to lipid droplet growth in the cytoplasm. In contrast, strong overexpression of -spectrin caused fat body atrophy and larval lethality. Overexpression of -spectrin also perturbed transport of dietary fat from the midgut to the fat body. This hypermorphic phenotype appears to be the result of blocking secretion of the lipid carrier lipophorin from fat cells. However, this midgut phenotype was never seen with spectrin loss of function, suggesting that spectrin is not normally required for lipophorin secretion or function. The -spectrin hypermorphic phenotype was ameliorated by co-overexpression of -spectrin. Based on the overexpression results here, we propose that -spectrin family members may be prone to hypermorphic effects (including effects on secretion) if their activity is not properly regulated.