Delta and Egfr expression are regulated by Importin-7/Moleskin in Drosophila wing development.
Delta and Egfr expression are regulated by Importin-7/Moleskin in Drosophila wing development.
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DOI：
10.1016/j.ydbio.2007.06.011
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发表时间：
2007-08
影响因子：
2.7
通讯作者：
A. Vrailas-Mortimer;N. Majumdar;Ginnene Middleton;Evan M Cooke;Daniel R. Marenda
中科院分区：
文献类型：
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作者：
A. Vrailas-Mortimer;N. Majumdar;Ginnene Middleton;Evan M Cooke;Daniel R. Marenda
果蝇 DIM-7（由鼹鼠皮基因 msk 编码）是脊椎动物 Importin-7 的直系同源物。 Importin-7 和 Msk/DIM-7 均充当核输入辅助因子，并参与多种信号转导途径的控制，包括 MAP 激酶激活（磷酸化）形式的直接核输入。我们进行了两次遗传缺陷筛查，以识别类似地改变眼睛和翅膀中 Msk 过度表达表型的缺陷。我们总共发现了 11 个缺陷，其中之一删除了 Delta 基因座。在本报告中，我们表明 Delta 功能丧失等位基因主要抑制发育中翅膀的 Msk 功能获得表型。我们发现 Msk 过表达会增加 Delta 蛋白表达和 Delta 转录，尽管单独 Msk 表达不足以激活 Delta 蛋白功能。我们还发现 Msk 过度表达会增加 Egfr 蛋白水平，并且 msk 基因功能是发育中的翅膀和眼睛中适当的 Egfr 表达所必需的。这些结果表明 Msk 在 Egfr 表达中具有新功能。我们讨论了这些数据对于 Egfr 和 Delta/Notch 信号传导整合的影响，特别是通过 MAP 激酶亚细胞定位的控制。
Drosophila DIM-7 (encoded by the moleskin gene, msk) is the orthologue of vertebrate Importin-7. Both Importin-7 and Msk/DIM-7 function as nuclear import cofactors, and have been implicated in the control of multiple signal transduction pathways, including the direct nuclear import of the activated (phosphorylated) form of MAP kinase. We performed two genetic deficiency screens to identify deficiencies that similarly modified Msk overexpression phenotypes in both eyes and wings. We identified 11 total deficiencies, one of which removes the Delta locus. In this report, we show that Delta loss-of-function alleles dominantly suppress Msk gain-of-function phenotypes in the developing wing. We find that Msk overexpression increases both Delta protein expression and Delta transcription, though Msk expression alone is not sufficient to activate Delta protein function. We also find that Msk overexpression increases Egfr protein levels, and that msk gene function is required for proper Egfr expression in both developing wings and eyes. These results indicate a novel function for Msk in Egfr expression. We discuss the implications of these data with respect to the integration of Egfr and Delta/Notch signaling, specifically through the control of MAP kinase subcellular localization.