University of Massachusetts Medical School, Department of Molecular, Cell and Cancer Biology, 364 Plantation Street, Worcester, MA 01605, USA.
Baylor College of Medicine, Program in Developmental Biology, Houston, TX 77030, USA.
Dev Cell. 2018 May 21;45(4):450-464.e3. doi: 10.1016/j.devcel.2018.04.020.
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 reactive oxygen species 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 Ras 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.
半胱天冬酶在细胞凋亡中具有重要作用。然而，它们也具有非凋亡功能，如凋亡诱导增殖（AiP），在此过程中，半胱天冬酶释放有丝分裂原以进行补偿性增殖，而不依赖于其凋亡作用。在这里，我们报告说，非传统肌球蛋白 Myo1D 已知参与左右发育，是果蝇 AiP 的重要介质。从机制上讲，Myo1D 将起始半胱天冬酶 Dronc 易位到上皮细胞的质膜基底侧，Dronc 在非凋亡方式下促进 NADPH 氧化酶 Duox 的激活，以产生活性氧和 AiP。我们提出质膜的基底侧构成了半胱天冬酶的非凋亡隔室。最后，Myo1D 促进了肿瘤 scrib Ras 模型的生长和侵袭。总之，我们确定了 Myo1D 促进 AiP 和肿瘤发生的新功能，并揭示了细胞将凋亡半胱天冬酶隔离在质膜非凋亡隔室中的机制。
