Mergliano Jaime, Minden Jonathan S
Department of Biological Sciences and Science and Technology Center for Light Microscope Imaging and Biotechnology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213, USA.
Development. 2003 Dec;130(23):5779-89. doi: 10.1242/dev.00824. Epub 2003 Oct 8.
Programmed cell death plays an essential role during Drosophila embryonic development. A stereotypic series of cellular changes occur during apoptosis, most of which are initiated by a caspase cascade that is triggered by a trio of proteins, RPR, HID and GRIM. The final step in apoptosis is engulfment of the cell corpse. To monitor cell engulfment in vivo, we developed a fluorogenic beta-galactosidase substrate that is cleaved by an endogenous, lysosomal beta-galactosidase activity. The pattern of cell engulfment in wild-type embryos correlated well with the known pattern of apoptosis. Surprisingly, the pattern of cell engulfment persisted in apoptosis-deficient embryos. We provide evidence for a caspase-independent engulfment process that affects the majority of cells expected to die in developing Drosophila embryos.
程序性细胞死亡在果蝇胚胎发育过程中起着至关重要的作用。在凋亡过程中会发生一系列刻板的细胞变化,其中大部分是由一组由RPR、HID和GRIM三种蛋白质触发的半胱天冬酶级联反应启动的。凋亡的最后一步是细胞尸体的吞噬。为了在体内监测细胞吞噬,我们开发了一种荧光β-半乳糖苷酶底物,该底物可被内源性溶酶体β-半乳糖苷酶活性切割。野生型胚胎中的细胞吞噬模式与已知的凋亡模式密切相关。令人惊讶的是,细胞吞噬模式在凋亡缺陷胚胎中持续存在。我们提供了证据,证明存在一种不依赖半胱天冬酶的吞噬过程,该过程影响果蝇胚胎发育过程中预期死亡的大多数细胞。