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Review
. 2010 Dec;22(6):889-95.
doi: 10.1016/j.ceb.2010.08.022. Epub 2010 Sep 16.

Distinct death mechanisms in Drosophila development

Hyung Don Ryoo  1 , Eric H Baehrecke
Affiliations
Review

Distinct death mechanisms in Drosophila development

Hyung Don Ryoo et al. Curr Opin Cell Biol. 2010 Dec.

Abstract

Apoptosis and autophagic cell death occur during Drosophila development, and recent advances in their mechanisms have been made. As in other organisms, apoptosis is executed by caspases. In living cells, caspases are kept in check through a combination of IAP-binding and proteolytic inhibition. Once a cell commits to apoptosis, phagocytes recognize them through the immuno-receptor-like proteins Draper and Simu, and initiate corpse engulfment. Drosophila research has significantly contributed to the idea that autophagy is required for certain forms of cell death, and that caspase function in autophagic cell death depends on cell context. Surprisingly, the cell corpse engulfment receptor Draper also functions in autophagic cell death. These advances facilitate our understanding of the cell death mechanisms in development and disease.

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Figures

Figure 1
Figure 1. Apoptosis in Drosophila
As in other organisms, caspases activation orchestrates apoptosis that involves cellular condensation, fragmentation and corpse engulfment. Caspases are made as inactive zymogens, but gain proteolytic activity after assembling into oligomeric complexes with its adaptor, Apaf1-related-killer. Recently, Tango7 was identified as another activator of caspases. In Drosophila, Inhibitors of Apoptosis Proteins (IAPs) play particularly visible roles in preventing caspase activation. Therefore, apoptosis requires the expression of IAP-antagonists, reaper, hid and grim. Phagocytes recognize apoptotic cells through surface proteins, Draper and Simu. Subsequently, a downstream signaling cascade that involves the kinase Shark and others involved in Ca2+ signaling are required to complete corpse engulfment.
Figure 2
Figure 2. Possible relationships between autophagy and capases during autophagic cell death
(A) Autophagy and caspases may function in a parallel genetic pathway, and this is supported by studies of fly salivary glands. (B) Autophagy and caspases may function in a common regulatory hierarchy. It is possible that either autophagy could regulate the activity of caspases, or caspases could regulate autophagy. Data to support these possible models have been provided in studies of fly ovaries.
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