TRiC/CCT chaperonins are essential for organ growth by interacting with insulin/TOR signaling in Drosophila
TRiC/CCT chaperonins are essential for organ growth by interacting with insulin/TOR signaling in Drosophila
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DOI：
10.1038/s41388-019-0754-1
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发表时间：
2019-06-13
期刊：
影响因子：
8
通讯作者：
Choi, Kwang-Wook
中科院分区：
文献类型：
--
作者：
Kim, Ah-Ram;Choi, Kwang-Wook
器官大小受细胞间信号传导调节，以促进细胞生长和增殖。TOR通路介导了器官生长中控制细胞大小和数量的关键信号机制。含有TCP-1 （CCT）的伴侣蛋白是一种辅助蛋白质折叠和功能的复合物，但其在动物发育中的作用在很大程度上是未知的。在这里，我们证明了CCT复合体是器官生长所必需的，通过与果蝇的TOR途径相互作用。CCT4的减少通过影响细胞大小和增殖导致生长缺陷。CCT4缺失导致眼盘形态发生沟前和翼盘翼囊内的细胞优先死亡。眼盘中任何CCT亚基的耗竭都会导致无头表型。活跃TOR信号的过度生长被CCT RNAi抑制。CCT复合体与TOR信号组件（包括TOR、Rheb和S6K）发生物理相互作用。CCT缺失导致S6K和S6磷酸化降低，而Akt磷酸化升高。胰岛素/TOR信号传导也是促进CCT复合体转录的必要和充分条件。我们的数据提供了证据，证明CCT复合体通过直接与TOR信号通路相互作用来调节器官生长。
Organ size is regulated by intercellular signaling for cell growth and proliferation. The TOR pathway mediates a key signaling mechanism for controlling cell size and number in organ growth. Chaperonin containing TCP-1 (CCT) is a complex that assists protein folding and function, but its role in animal development is largely unknown. Here we show that the CCT complex is required for organ growth by interacting with the TOR pathway in Drosophila. Reduction of CCT4 results in growth defects by affecting both cell size and proliferation. Loss of CCT4 causes preferential cell death anterior to the morphogenetic furrow in the eye disc and within wing pouch in the wing disc. Depletion of any CCT subunit in the eye disc results in headless phenotype. Overgrowth by active TOR signaling is suppressed by CCT RNAi. The CCT complex physically interacts with TOR signaling components including TOR, Rheb, and S6K. Loss of CCT leads to decreased phosphorylation of S6K and S6 while increasing phosphorylation of Akt. Insulin/TOR signaling is also necessary and sufficient for promoting CCT complex transcription. Our data provide evidence that the CCT complex regulates organ growth by directly interacting with the TOR signaling pathway.