Kang Yunsik, Neuman Sarah D, Bashirullah Arash
Division of Pharmaceutical Sciences, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI, 53705-2222, USA.
Laboratory of Genetics Graduate Program, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Nat Commun. 2017 Sep 19;8(1):603. doi: 10.1038/s41467-017-00693-3.
Caspases perform critical functions in both living and dying cells; however, how caspases perform physiological functions without killing the cell remains unclear. Here we identify a novel physiological function of caspases at the cortex of Drosophila salivary glands. In living glands, activation of the initiator caspase dronc triggers cortical F-actin dismantling, enabling the glands to stretch as they accumulate secreted products in the lumen. We demonstrate that tango7, not the canonical Apaf-1-adaptor dark, regulates dronc activity at the cortex; in contrast, dark is required for cytoplasmic activity of dronc during salivary gland death. Therefore, tango7 and dark define distinct subcellular domains of caspase activity. Furthermore, tango7-dependent cortical dronc activity is initiated by a sublethal pulse of the inhibitor of apoptosis protein (IAP) antagonist reaper. Our results support a model in which biological outcomes of caspase activation are regulated by differential amplification of IAP antagonists, unique caspase adaptor proteins, and mutually exclusive subcellular domains of caspase activity.Caspases are known for their role in cell death, but they can also participate in other physiological functions without killing the cells. Here the authors show that unique caspase adaptor proteins can regulate caspase activity within mutually-exclusive and independently regulated subcellular domains.
半胱天冬酶在活细胞和濒死细胞中都发挥着关键作用;然而,半胱天冬酶如何在不杀死细胞的情况下执行生理功能仍不清楚。在此,我们确定了半胱天冬酶在果蝇唾液腺皮质中的一种新的生理功能。在活的腺体中,起始半胱天冬酶dronc的激活会触发皮质F-肌动蛋白的拆解,使腺体在管腔中积累分泌产物时能够伸展。我们证明,是tango7而非经典的Apaf-1衔接蛋白dark调节皮质处的dronc活性;相反,在唾液腺死亡过程中,dark是dronc细胞质活性所必需的。因此,tango7和dark定义了半胱天冬酶活性的不同亚细胞结构域。此外,tango7依赖的皮质dronc活性是由凋亡抑制蛋白(IAP)拮抗剂收割者的亚致死脉冲启动的。我们的结果支持这样一种模型,即半胱天冬酶激活的生物学结果是由IAP拮抗剂、独特的半胱天冬酶衔接蛋白以及相互排斥的半胱天冬酶活性亚细胞结构域的差异放大来调节的。半胱天冬酶因其在细胞死亡中的作用而闻名,但它们也可以在不杀死细胞的情况下参与其他生理功能。在此,作者表明独特的半胱天冬酶衔接蛋白可以在相互排斥且独立调节的亚细胞结构域内调节半胱天冬酶活性。