Department of Molecular Biosciences, Northwestern University, Evanston, IL, 60208, USA.
Nat Commun. 2019 Mar 4;10(1):1031. doi: 10.1038/s41467-019-09009-z.
Although well known for its role in apoptosis, the executioner caspase DrICE has a non-apoptotic function that is required for elongation of the epithelial tubes of the Drosophila tracheal system. Here, we show that DrICE acts downstream of the Hippo Network to regulate endocytic trafficking of at least four cell polarity, cell junction and apical extracellular matrix proteins involved in tracheal tube size control: Crumbs, Uninflatable, Kune-Kune and Serpentine. We further show that tracheal cells are competent to undergo apoptosis, even though developmentally-regulated DrICE function rarely kills tracheal cells. Our results reveal a developmental role for caspases, a pool of DrICE that co-localizes with Clathrin, and a mechanism by which the Hippo Network controls endocytic trafficking. Given reports of in vitro regulation of endocytosis by mammalian caspases during apoptosis, we propose that caspase-mediated regulation of endocytic trafficking is an evolutionarily conserved function of caspases that can be deployed during morphogenesis.
尽管凋亡效应蛋白酶 DrICE 以其在凋亡中的作用而闻名，但它也具有非凋亡功能，这对于果蝇气管系统的上皮管的伸长是必需的。在这里，我们表明 DrICE 作为 Hippo 网络的下游因子，调节至少四种参与气管管大小控制的细胞极性、细胞连接和顶端细胞外基质蛋白的内吞运输：Crumb、Uninflatable、Kune-Kune 和 Serpentine。我们进一步表明，气管细胞有能力进行凋亡，尽管发育调控的 DrICE 功能很少杀死气管细胞。我们的结果揭示了 Caspases 在发育中的作用，一种与网格蛋白共定位的 DrICE 池，以及 Hippo 网络控制内吞运输的机制。鉴于有报道称在体外凋亡过程中哺乳动物 Caspases 调节内吞作用，我们提出 Caspase 介导的内吞运输调节是 Caspases 的一种进化保守功能，可在形态发生过程中被利用。
