A Switch-like Activation Relay of EGFR-ERK Signaling Regulates a Wave of Cellular Contractility for Epithelial Invagination
A Switch-like Activation Relay of EGFR-ERK Signaling Regulates a Wave of Cellular Contractility for Epithelial Invagination
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DOI：
10.1016/j.devcel.2018.06.004
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发表时间：
2018-07-16
影响因子：
11.8
通讯作者：
Hayashi, Shigeo
中科院分区：
文献类型：
--
作者：
Ogura, Yosuke;Wen, Fu-Lai;Hayashi, Shigeo
细胞外信号调节激酶 (ERK) 信号传导的动力学是其在细胞分化、细胞增殖和细胞运动中多功能功能的基础。果蝇的经典研究表明，表皮生长因子受体 (EGFR)-ERK 信号传导的梯度对于这些细胞反应至关重要。然而，我们通过实时监测 ERK 激活来挑战这一观点；我们发现，类似开关的 ERK 激活对于果蝇气管基板的内陷运动至关重要。这种类似开关的 ERK 激活源于 EGFR-ERK 信号传导的正反馈调节以及气管细胞之间 EGFR-ERK 信号传导的中继。关键转录因子 Trachealess (Trh) 允许调节中继的迭代，并且 ERK 激活在 trh 突变体中分级。基于这些观察结果的数学模型以及 ERK 激活动力学和肌球蛋白之间的分子联系表明，中继机制有效地促进上皮内陷，而梯度机制则不然。
The dynamics of extracellular signal-regulated kinase (ERK) signaling underlies its versatile functions in cell differentiation, cell proliferation, and cell motility. Classical studies in Drosophila established that a gradient of epidermal growth factor receptor (EGFR)-ERK signaling is essential for these cellular responses. However, we challenge this view by the real-time monitoring of ERK activation; we show that a switch-like ERK activation is essential for the invagination movement of the Drosophila tracheal placode. This switch-like ERK activation stems from the positive feedback regulation of the EGFR-ERK signaling and a resultant relay of EGFR-ERK signaling among tracheal cells. A key transcription factor Trachealess (Trh) permissively regulates the iteration of the relay, and the ERK activation becomes graded in trh mutant. A mathematical model based on these observations and a molecular link between ERK activation dynamics and myosin shows that the relay mechanism-efficiently promotes epithelial invagination while the gradient mechanism does not.