Drosophila ZIP13 is posttranslationally regulated by iron-mediated stabilization
Drosophila ZIP13 is posttranslationally regulated by iron-mediated stabilization
复制标题
果蝇 ZIP13 通过铁介导的稳定进行翻译后调节
DOI：
10.1016/j.bbamcr.2019.06.009
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发表时间：
2019
影响因子：
5.1
通讯作者：
Zhou Bing
中科院分区：
文献类型：
--
作者：
Xu Junxuan;Wan Zhihui;Zhou Bing
果蝇azip13 （dZIP13, CG7816/ZIP99C）属于SLC39A家族，与果蝇铁稳态有关。在这项研究中，我们发现dZIP13水平受到铁的强烈调节。除了在mRNA水平上对铁有轻微反应外，dZIP13在蛋白质水平上受到强烈调节。当dZIP13在酵母（酿酒酵母）中表达时，铁的翻译后调控也会发生。铁的作用是稳定dZIP13。dZIP7 （CG10449/ Catsup）和dZIP13之间的结构域交换实验表明，dZIP13的n端介导了这一铁调控过程。系统发育序列比较和结构建模揭示了潜在的铁结合残基，由体外铁结合试验证实。这些在n端潜在的铁结合位点的突变，以及dZIP13的c端可能的铁结合位点的突变，完全消除了酵母和果蝇中铁依赖性上调。dZIP13的铁响应性与其在铁稳态中的关键作用是一致的。我们推测，dZIP13调控过程和IRE/ irp控制的铁蛋白产生过程共同作用，以更好地应对苍蝇体内的铁补充。
DrosophilaZIP13 (dZIP13, CG7816/ZIP99C) belongs to the SLC39A family and is connected to iron homeostasis in the fruit fly. In this study, we show that dZIP13 level is strongly regulated by iron. In addition to a mild response to iron at the mRNA level, dZIP13 is strongly regulated at the protein level. This posttranslational regulation by iron also happens when dZIP13 is expressed in the yeastSaccharomyces cerevisiae. Iron functions to stabilize dZIP13. Domain-swapping experiments between dZIP7 (CG10449/ Catsup) and dZIP13 suggest that the N-terminus of dZIP13 is necessary to mediate this iron regulatory process. Phylogenetic sequence comparison and structural modeling reveal potential iron-binding residues, confirmed byin vitroiron binding assays. Mutations of these potential iron binding sites at the N-terminus, as well as a likely iron binding site at the C-terminus of dZIP13, completely abolish the iron-dependent upregulation in the yeast and the fruit fly. Iron-responsiveness of dZIP13 is consistent with its key role in iron homeostasis. We speculate that this process of dZIP13 regulation, and that of IRE/IRP-controlled ferritin production, work together to better cope with iron repletion in the fly.