Published 13 March 2006. doi:10.1083/jcb.200512126
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 6, 809-815
The Drosophila melanogaster Apaf-1 homologue ARK is required for most, but not all, programmed cell death
Kathryn Mills1,
Tasman Daish1,
Kieran F. Harvey2,
Cathie M. Pfleger2,
Iswar K. Hariharan2, and
Sharad Kumar1
1 Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, Australia 5000
2 Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720
Correspondence to Sharad Kumar: sharad.kumar{at}imvs.sa.gov.au
Abstract
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.
Abbreviations used in this paper: AO, acridine orange; CARD, caspase recruitment domain; CNS, central nervous system; ELAV, embryonic lethal abnormal visual protein; PCD, programmed cell death; RPF, relative to puparium formation; WT, wild-type.
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