Ferritin Is Required in Multiple Tissues during Drosophila melanogaster Development.
Ferritin Is Required in Multiple Tissues during Drosophila melanogaster Development.
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DOI：
10.1371/journal.pone.0133499
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Riesgo-Escovar JR
中科院分区：
文献类型：
--
作者：
González-Morales N;Mendoza-Ortíz MÁ;Blowes LM;Missirlis F;Riesgo-Escovar JR
在果蝇中，铁被储存在细胞内膜系统中，这个蛋白质笼由两种类型的24个铁蛋白亚基(Fer1HCH和Fer2LCH)以1：1的化学计量比形成。在幼虫体内，铁蛋白聚集在中肠、血淋巴、花环、心包细胞和神经系统中。在这里，我们提供了对Fer1HCH、Fer2LCH和这两个基因同时突变的胚胎表型的分析。任何一个基因的突变或两个基因的缺失都会导致一组相似的角质层胚胎表型，从角质层不沉积到与生殖带回缩、背部闭合和头部退化相关的缺陷。部分铁蛋白突变体具有胚胎神经系统，伴有腹神经索断裂、错误的轴突投射和大脑畸形。铁蛋白突变体死于异位的细胞凋亡事件。此外，我们还发现，铁蛋白对母体的贡献，不同地反映了母体的铁储存，在早期发育中使用。我们还评估了COPII从内质网到高尔基体的运输受阻所产生的表型，提供了分泌途径，以及对异位表达和荧光标记的Fer1HCH和Fer2LCH的分析。总体而言，我们的结果与昆虫铁蛋白结合了三个功能：铁储存、细胞间铁运输和保护免受铁诱导的氧化应激是一致的。这些功能在果蝇胚胎发育的多个组织中都是必需的。
In Drosophila melanogaster, iron is stored in the cellular endomembrane system inside a protein cage formed by 24 ferritin subunits of two types (Fer1HCH and Fer2LCH) in a 1:1 stoichiometry. In larvae, ferritin accumulates in the midgut, hemolymph, garland, pericardial cells and in the nervous system. Here we present analyses of embryonic phenotypes for mutations in Fer1HCH, Fer2LCH and in both genes simultaneously. Mutations in either gene or deletion of both genes results in a similar set of cuticular embryonic phenotypes, ranging from non-deposition of cuticle to defects associated with germ band retraction, dorsal closure and head involution. A fraction of ferritin mutants have embryonic nervous systems with ventral nerve cord disruptions, misguided axonal projections and brain malformations. Ferritin mutants die with ectopic apoptotic events. Furthermore, we show that ferritin maternal contribution, which varies reflecting the mother’s iron stores, is used in early development. We also evaluated phenotypes arising from the blockage of COPII transport from the endoplasmic reticulum to the Golgi apparatus, feeding the secretory pathway, plus analysis of ectopically expressed and fluorescently marked Fer1HCH and Fer2LCH. Overall, our results are consistent with insect ferritin combining three functions: iron storage, intercellular iron transport, and protection from iron-induced oxidative stress. These functions are required in multiple tissues during Drosophila embryonic development.