Plasma Membrane Localization of Apoptotic Caspases for Non-apoptotic Functions.
Plasma Membrane Localization of Apoptotic Caspases for Non-apoptotic Functions.
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DOI：
10.1016/j.devcel.2018.04.020
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发表时间：
2018-05-21
影响因子：
11.8
通讯作者：
Bergmann A
中科院分区：
文献类型：
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作者：
Amcheslavsky A;Wang S;Fogarty CE;Lindblad JL;Fan Y;Bergmann A
Caspases 的最佳特性是其在细胞凋亡中的功能。然而，它们也具有非凋亡功能，例如凋亡诱导增殖 (AiP)，其中半胱天冬酶释放有丝分裂原以进行代偿性增殖，而与凋亡作用无关。在这里，我们报告说，非常规肌球蛋白 Myo1D 因其参与左/右发育而闻名，是果蝇 AiP 的重要介质。从机制上讲，Myo1D 将起始 caspase Dronc 易位到上皮细胞质膜的基底侧，其中 Dronc 促进 NADPH 氧化酶 Duox 的激活，以非凋亡方式产生 ROS 和 AiP。我们认为质膜的基底侧构成半胱天冬酶的非凋亡区室。最后，Myo1D 促进肿瘤 Scrib RasV12 模型的肿瘤生长和侵袭性。我们共同确定了 Myo1D 在 AiP 和肿瘤发生中的新功能，并揭示了细胞在质膜非凋亡区室中隔离凋亡 caspase 的机制。阿姆切斯拉夫斯基等人。提供了一种细胞激活半胱天冬酶的机制，而不会产生细胞凋亡的有害后果。在果蝇中，非常规肌球蛋白 Myo1D 将启动子 caspase Dronc 定位于上皮细胞质膜的基底侧。在这里，Dronc 可以实现非凋亡功能，例如凋亡诱导的增殖。
Caspases are best characterized for their function in apoptosis. However, they also have non-apoptotic functions such as apoptosis-induced proliferation (AiP) where caspases release mitogens for compensatory proliferation independently of their apoptotic role. Here, we report that the unconventional myosin, Myo1D, which is known for its involvement in left/right development, is an important mediator of AiP in Drosophila. Mechanistically, Myo1D translocates the initiator caspase Dronc to the basal side of the plasma membrane of epithelial cells where Dronc promotes the activation of the NADPH-oxidase Duox for ROS generation and AiP in a non-apoptotic manner. We propose that the basal side of the plasma membrane constitutes a non-apoptotic compartment for caspases. Finally, Myo1D promotes tumor growth and invasiveness of the neoplastic scrib RasV12 model. Together, we identified a new function of Myo1D for AiP and tumorigenesis, and reveal a mechanism by which cells sequester apoptotic caspases in a non-apoptotic compartment at the plasma membrane. Amcheslavsky et al. provide a mechanism by which cells activate caspases without the detrimental consequences of apoptosis. In Drosophila, the unconventional myosin Myo1D localizes the initiator caspase Dronc to the basal side of the plasma membrane of epithelial cells. Here, Dronc can fulfil non-apoptotic functions such as apoptosis-induced proliferation.