The novel Smad protein Expansion regulates the receptor tyrosine kinase pathway to control Drosophila tracheal tube size
The novel Smad protein Expansion regulates the receptor tyrosine kinase pathway to control Drosophila tracheal tube size
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DOI：
10.1016/j.ydbio.2014.06.016
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发表时间：
2014-09-01
影响因子：
2.7
通讯作者：
Jiang, Lan
中科院分区：
文献类型：
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作者：
Iordanou, Ekaterini;Chandran, Rachana R.;Jiang, Lan
具有不同形状和尺寸的管对于许多管状器官的正常功能至关重要。在这里，我们描述了一种独特的表型，该表型是由一种新型的、进化上保守的果蝇 Smad 样蛋白 Expansion 的丢失引起的。在扩张突变体中，单细胞和细胞内气管分支形成具有增大的顶膜的气泡状囊肿。单细胞管中的囊肿是顶端腔的扩大，而细胞内管中的囊肿是细胞质液泡样区室。扩增突变体中的囊肿表型与果蝇 III 型受体酪氨酸磷酸酶 (RPTP)、Ptp4E 和 Ptp10D 双突变体中观察到的囊肿表型相似，但较弱。 Ptp4E 和 Ptp10D 负向调节受体酪氨酸激酶 (RTK) 通路，特别是上皮生长因子受体 (EGFR) 和成纤维细胞生长因子受体/呼吸 (FGFR、Btl) 信号传导，以维持单细胞和细胞内管的适当大小。我们发现 Exp 在基因上与 RTK 信号（RPTP 的下游靶标）相互作用。扩增突变体中的囊肿大小和数量通过增加 RTK 信号传导而增强，并通过减少 RTK 信号传导而抑制。遗传相互作用研究强烈表明，Exp 负向调节 RTK（EGFR、Btl）信号传导，以确保适当的试管尺寸。 Smad 蛋白通常作为转化生长因子-β（TGF-β、DPP）信号通路的中间成分发挥作用。然而，没有观察到扩增与 TGF-β (DPP) 信号传导之间存在明显的遗传相互作用。因此，Expansion 不具有典型 Smad 蛋白的功能。扩张表型证明了 Smad 样蛋白在上皮管形成中的新作用。 (C) 2014 Elsevier Inc. 保留所有权利。
Tubes with distinct shapes and sizes are critical for the proper function of many tubular organs. Here we describe a unique phenotype caused by the loss of a novel, evolutionarily-conserved, Drosophila Smad-like protein, Expansion. In expansion mutants, unicellular and intracellular tracheal branches develop bubble-like cysts with enlarged apical membranes. Cysts in unicellular tubes are enlargements of the apical lumen, whereas cysts in intracellular tubes are cytoplasmic vacuole-like compartments. The cyst phenotype in expansion mutants is similar to, but weaker than, that observed in double mutants of Drosophila type III receptor tyrosine phosphatases (RPTPs), Ptp4E and Ptp10D. Ptp4E and Ptp10D negatively regulate the receptor tyrosine kinase (RTK) pathways, especially epithelial growth factor receptor (EGFR) and fibroblast growth factor receptor/breathless (FGFR, Btl) signaling to maintain the proper size of unicellular and intracellular tubes. We show Exp genetically interacts with RTK signaling, the downstream targets of RPTPs. Cyst size and number in expansion mutants is enhanced by increased RTK signaling and suppressed by reduced RTK signaling. Genetic interaction studies strongly suggest that Exp negatively regulates RTK (EGFR, Btl) signaling to ensure proper tube sizes. Smad proteins generally function as intermediate components of the transforming growth factor-beta (TGF-beta, DPP) signaling pathway. However, no obvious genetic interaction between expansion and TGF-beta (DPP) signaling was observed. Therefore, Expansion does not function as a typical Smad protein. The expansion phenotype demonstrates a novel role for Smad-like proteins in epithelial tube formation. (C) 2014 Elsevier Inc. All rights reserved.