grim promotes programmed cell death of Drosophila microchaete glial cells.
The Inhibitor of apoptosis (IAP) antagonists Reaper (Rpr), Grim and Hid are central regulators of developmental apoptosis in Drosophila. Ectopic expression of each is sufficient to trigger apoptosis, and hid and rpr have been shown to be important for programmed cell death (PCD). To investigate the role for grim in PCD, a grim null mutant was generated. grim was not a key proapoptotic gene for embryonic PCD, confirming that grim cooperates with rpr and hid in embryogenesis. In contrast, PCD of glial cells in the microchaete lineage required grim, identifying a death process dependent upon endogenous grim. Grim associates with mitochondria and has been shown to activate a mitochondrial death pathway distinct from IAP antagonization; therefore, the Drosophila bcl-2 genes buffy and debcl were investigated for genetic interaction with grim. Loss of buffy led to microchaete glial cell survival and suppressed death in the eye induced by ectopic Grim. This is the first example of a developmental PCD process influenced by buffy, and places buffy in a proapoptotic role. PCD of microchaete glial cells represents an exceptional opportunity to study the mitochondrial proapoptotic process induced by Grim.
Wu
Julie N
JN
Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300, USA.
Nguyen
Nguyen
N
Aghazarian
Maral
M
Tan
Ying
Y
Sevrioukov
Evgueni A
EA
Mabuchi
Megumu
M
Tang
Wei
W
Monserrate
Jessica P
JP
White
Kristin
K
Brachmann
Carrie Baker
CB
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D019070:Cell Lineage; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
C477358:Buffy protein, Drosophila; D029721:Drosophila Proteins; D009479:Neuropeptides; D019253:Proto-Oncogene Proteins c-bcl-2; C108881:grim protein, Drosophila