Autophagy genes function in apoptotic cell corpse clearance during C. elegans embryonic development

被引:41
|
作者
Huang, Shuyi [1 ,2 ]
Jia, Kailiang [2 ]
Wang, Ying [3 ]
Zhou, Zheng [3 ]
Levine, Beth [1 ,2 ,4 ,5 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA
[3] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA
[4] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA
[5] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA
关键词
autophagy; apoptotic corpse clearance; C; elegans; embryogenesis; cell death; PHAGOSOME MATURATION; MEMBRANE TRAFFICKING; BECLIN; ENGULFMENT; REMOVAL; PATHWAY; PROTEIN; DEGRADATION; RECEPTOR; DEATH;
D O I
10.4161/auto.22352
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Efficient apoptotic corpse clearance is essential for metazoan development and adult tissue homeostasis. Several autophagy proteins have been previously shown to function in apoptotic cell clearance; however, it remains unknown whether autophagy genes are essential for efficient apoptotic corpse clearance in the developing embryo. Here we show that, in Caenorhabditis elegans embryos, loss-of-function mutations in several autophagy genes that act at distinct steps in the autophagy pathway resulted in increased numbers of cell corpses and delayed cell corpse clearance. Further analysis of embryos with a null mutation in bec-1, the C. elegans ortholog of yeast VPS30/ATG6/mammalian beclin 1 (BECN1), revealed normal phosphatidylserine exposure on dying cells. Moreover, the corpse clearance defects of bec-1(ok691) embryos were rescued by BEC-1 expression in engulfing cells, and bec-1(ok691) enhanced corpse clearance defects in nematodes with simultaneous mutations in the engulfment genes, ced-1, ced-6 or ced-12. Together, these data demonstrate that autophagy proteins play an important role in cell corpse clearance during nematode embryonic development, and likely function in parallel to known pathways involved in corpse removal.
引用
收藏
页码:138 / 149
页数:12
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