Caspases function in autophagic programmed cell death in Drosophila.
Self-digestion of cytoplasmic components is the hallmark of autophagic programmed cell death. This auto-degradation appears to be distinct from what occurs in apoptotic cells that are engulfed and digested by phagocytes. Although much is known about apoptosis, far less is known about the mechanisms that regulate autophagic cell death. Here we show that autophagic cell death is regulated by steroid activation of caspases in Drosophila salivary glands. Salivary glands exhibit some morphological changes that are similar to apoptotic cells, including fragmentation of the cytoplasm, but do not appear to use phagocytes in their degradation. Changes in the levels and localization of filamentous Actin, alpha-Tubulin, alpha-Spectrin and nuclear Lamins precede salivary gland destruction, and coincide with increased levels of active Caspase 3 and a cleaved form of nuclear Lamin. Mutations in the steroid-regulated genes beta FTZ-F1, E93, BR-C and E74A that prevent salivary gland cell death possess altered levels and localization of filamentous Actin, alpha-Tubulin, alpha-Spectrin, nuclear Lamins and active Caspase 3. Inhibition of caspases, by expression of either the caspase inhibitor p35 or a dominant-negative form of the initiator caspase Dronc, is sufficient to inhibit salivary gland cell death, and prevent changes in nuclear Lamins and alpha-Tubulin, but not to prevent the reorganization of filamentous Actin. These studies suggest that aspects of the cytoskeleton may be required for changes in dying salivary glands. Furthermore, caspases are not only used during apoptosis, but also function in the regulation of autophagic cell death.
Martin
Damali N
DN
Center for Biosystems Research, University of Maryland Biotechnology Institute, and Department of Cell Biology, University of Maryland, College Park, Maryland 20742, USA.
Baehrecke
Eric H
EH
D000199:Actins / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D020169:Caspases / Q000502:physiology*; D004330:Drosophila / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics; D029721:Drosophila Proteins / Q000378:metabolism; D017344:Genes, Insect; D009154:Mutation; D012469:Salivary Glands / Q000166:cytology / Q000201:enzymology; D013256:Steroids / Q000378:metabolism
D000199:Actins; D029721:Drosophila Proteins; D013256:Steroids; D020169:Caspases