Cell Competition Is Driven by Autophagy
Cell Competition Is Driven by Autophagy
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DOI：
10.1016/j.devcel.2019.08.018
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发表时间：
2019-10-07
影响因子：
11.8
通讯作者：
Igaki, Tatsushi
中科院分区：
文献类型：
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作者：
Nagata, Rina;Nakamura, Mai;Igaki, Tatsushi
细胞竞争是一种质量控制过程，通过细胞与细胞之间的相互作用，有选择地将不适合的细胞从生长组织中剔除。尽管进行了广泛的机制研究，但触发细胞消除的机制一直难以捉摸。在这里，通过对果蝇的遗传筛选，我们发现V-ATPase是自噬的一个必不可少的因素，它是触发细胞竞争所必需的。引人注目的是，自噬在野生型“赢家”细胞附近的潜在“失败者”细胞中特定地升高，而阻止失败者细胞中的自噬就取消了它们的消除。从机制上讲，自噬上调通过NFkB上调促凋亡基因HID，而上调的HID与JNK信号协同有效地诱导失败者死亡。至关重要的是，这一机制通常适用于由细胞间蛋白质合成差异引起的细胞竞争。我们的发现建立了一种常见的细胞竞争机制，即蛋白质合成较高的细胞在邻近细胞中诱导自噬，从而消除不适合的细胞。
Cell competition is a quality control process that selectively eliminates unfit cells from the growing tissue via cell-cell interaction. Despite extensive mechanistic studies, the mechanism by which cell elimination is triggered has been elusive. Here, through a genetic screen in Drosophila, we discover that V-ATPase, an essential factor for autophagy, is required for triggering cell competition. Strikingly, autophagy is specifically elevated in prospective "loser" cells nearby wild-type "winner" cells, and blocking autophagy in loser cells abolishes their elimination. Mechanistically, elevated autophagy upregulates a proapoptotic gene hid through NFkB, and the elevated hid cooperates with JNK signaling to effectively induce loser's death. Crucially, this mechanism generally applies to cell competition caused by differences in protein synthesis between cells. Our findings establish a common mechanism of cell competition whereby cells with higher protein synthesis induce autophagy in their neighboring cells, leading to elimination of unfit cells.