Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan.
Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan.
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发表时间：
2001-06
期刊：
影响因子：
4.6
通讯作者：
N. Tolwinski;E. Wieschaus
中科院分区：
文献类型：
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作者：
N. Tolwinski;E. Wieschaus
黑腹犰狳在发育过程中扮演着两个不同的角色。它是粘附连接的一个组成部分，在响应无翼信号时作为转录激活因子发挥作用。在目前的模型中，无翼信号导致细胞质犰狳的稳定，允许它进入细胞核，在那里它可以激活转录。然而，核进出口的机制仍有待阐明。在这项研究中，我们发现犰狳的两个功能获得等位基因通过不同的机制激活无翼信号。S10等位基因先前被发现定位于细胞核，在那里它激活转录。相反，Delta Arm等位基因定位于质膜，并迫使内源性Arm进入细胞核。因此，Delta Arm依赖于Arm功能性内源性等位基因的存在来激活转录。我们发现Delta臂可能通过将轴蛋白滴定到膜上而起作用，这表明它作为细胞质锚点使臂远离细胞核。在轴蛋白突变体中，Arm定位于细胞核。我们发现核保留依赖于dTCF/穿山甲。这表明Arm的细胞分布受锚定系统控制，其中各种核和细胞质结合伙伴决定其定位。
Drosophila melanogaster Armadillo plays two distinct roles during development. It is a component of adherens junctions, and functions as a transcriptional activator in response to Wingless signaling. In the current model, Wingless signal causes stabilization of cytoplasmic Armadillo allowing it to enter the nucleus where it can activate transcription. However, the mechanism of nuclear import and export remains to be elucidated. In this study, we show that two gain-of-function alleles of Armadillo activate Wingless signaling by different mechanisms. The S10 allele was previously found to localize to the nucleus, where it activates transcription. In contrast, the Delta Arm allele localizes to the plasma membrane, and forces endogenous Arm into the nucleus. Therefore, Delta Arm is dependent on the presence of a functional endogenous allele of arm to activate transcription. We show that Delta Arm may function by titrating Axin protein to the membrane, suggesting that it acts as a cytoplasmic anchor keeping Arm out of the nucleus. In axin mutants, Arm is localized to the nuclei. We find that nuclear retention is dependent on dTCF/Pangolin. This suggests that cellular distribution of Arm is controlled by an anchoring system, where various nuclear and cytoplasmic binding partners determine its localization.