The Drosophila melanogaster Apaf-1 homologue ARK is required for most, but not all, programmed cell death.
The Apaf-1 protein is essential for cytochrome c-mediated caspase-9 activation in the intrinsic mammalian pathway of apoptosis. Although Apaf-1 is the only known mammalian homologue of the Caenorhabditis elegans CED-4 protein, the deficiency of apaf-1 in cells or in mice results in a limited cell survival phenotype, suggesting that alternative mechanisms of caspase activation and apoptosis exist in mammals. In Drosophila melanogaster, the only Apaf-1/CED-4 homologue, ARK, is required for the activation of the caspase-9/CED-3-like caspase DRONC. Using specific mutants that are deficient for ark function, we demonstrate that ARK is essential for most programmed cell death (PCD) during D. melanogaster development, as well as for radiation-induced apoptosis. ark mutant embryos have extra cells, and tissues such as brain lobes and wing discs are enlarged. These tissues from ark mutant larvae lack detectable PCD. During metamorphosis, larval salivary gland removal was severely delayed in ark mutants. However, PCD occurred normally in the larval midgut, suggesting that ARK-independent cell death pathways also exist in D. melanogaster.
Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, Australia 5000.
Kathryn
K
Mills
Tasman
T
Daish
Kieran F
KF
Harvey
Cathie M
CM
Pfleger
Iswar K
IK
Hariharan
Sharad
S
Kumar
D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000254:growth & development*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental / Q000235:genetics* / Q000528:radiation effects; D005804:Genes, Lethal / Q000235:genetics; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008675:Metamorphosis, Biological / Q000235:genetics; D009154:Mutation / Q000235:genetics / Q000528:radiation effects; D011839:Radiation, Ionizing; D012469:Salivary Glands / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D029721:Drosophila Proteins; C400550:dark protein, Drosophila