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CycD/Cdk4 和 Dpp 信号中的不连续性激活果蝇翅盘中的 TORC1。

CycD/Cdk4 and Discontinuities in Dpp Signaling Activate TORC1 in the Drosophila Wing Disc.

机构信息

German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg University, 69120 Heidelberg, Germany.

German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg University, 69120 Heidelberg, Germany.

出版信息

Dev Cell. 2017 Aug 21;42(4):376-387.e5. doi: 10.1016/j.devcel.2017.07.019.

Abstract

The molecular mechanisms regulating animal tissue size during development are unclear. This question has been extensively studied in the Drosophila wing disc. Although cell growth is regulated by the kinase TORC1, no readout exists to visualize TORC1 activity in situ in Drosophila. Both the cell cycle and the morphogen Dpp are linked to tissue growth, but whether they regulate TORC1 activity is not known. We develop here an anti-phospho-dRpS6 antibody that detects TORC1 activity in situ. We find, unexpectedly, that TORC1 activity in the wing disc is patchy. This is caused by elevated TORC1 activity at the cell cycle G/S transition due to CycD/Cdk4 phosphorylating TSC1/2. We find that TORC1 is also activated independently of CycD/Cdk4 when cells with different levels of Dpp signaling or Brinker protein are juxtaposed. We thereby characterize the spatial distribution of TORC1 activity in a developing organ.

摘要

在发育过程中调节动物组织大小的分子机制尚不清楚。这个问题在果蝇翅膀盘中得到了广泛研究。尽管细胞生长受激酶 TORC1 调节,但在果蝇中没有可用于原位可视化 TORC1 活性的读数。细胞周期和形态发生因子 Dpp 都与组织生长有关,但它们是否调节 TORC1 活性尚不清楚。我们在这里开发了一种抗磷酸化-dRpS6 抗体,可用于原位检测 TORC1 活性。出乎意料的是,我们发现翅膀盘中的 TORC1 活性呈斑片状。这是由于 CycD/Cdk4 磷酸化 TSC1/2 导致细胞周期 G/S 转换时 TORC1 活性升高所致。我们发现,当具有不同 Dpp 信号或 Brinker 蛋白水平的细胞并置时,TORC1 也会独立于 CycD/Cdk4 激活。因此,我们描述了在发育器官中 TORC1 活性的空间分布。

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