Document Detail

The Bax/Bak ortholog in Drosophila, Debcl, exerts limited control over programmed cell death.
MedLine Citation:
PMID:  19088092     Owner:  NLM     Status:  MEDLINE    
Bcl-2 family members are pivotal regulators of programmed cell death (PCD). In mammals, pro-apoptotic Bcl-2 family members initiate early apoptotic signals by causing the release of cytochrome c from the mitochondria, a step necessary for the initiation of the caspase cascade. Worms and flies do not show a requirement for cytochrome c during apoptosis, but both model systems express pro- and anti-apoptotic Bcl-2 family members. Drosophila encodes two Bcl-2 family members, Debcl (pro-apoptotic) and Buffy (anti-apoptotic). To understand the role of Debcl in Drosophila apoptosis, we produced authentic null alleles at this locus. Although gross development and lifespans were unaffected, we found that Debcl was required for pruning cells in the developing central nervous system. debcl genetically interacted with the ced-4/Apaf1 counterpart dark, but was not required for killing by RHG (Reaper, Hid, Grim) proteins. We found that debcl(KO) mutants were unaffected for mitochondrial density or volume but, surprisingly, in a model of caspase-independent cell death, heterologous killing by murine Bax required debcl to exert its pro-apoptotic activity. Therefore, although debcl functions as a limited effector of PCD during normal Drosophila development, it can be effectively recruited for killing by mammalian members of the Bcl-2 gene family.
Kathleen A Galindo; Wan-Jin Lu; Jae H Park; John M Abrams
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-12-15
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  136     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-23     Completed Date:  2009-03-18     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  275-83     Citation Subset:  IM    
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MeSH Terms
Animals, Genetically Modified
Apoptosis / genetics,  physiology*
Autophagy / genetics,  physiology
Base Sequence
Central Nervous System / cytology,  embryology
DNA Primers / genetics
Drosophila / cytology*,  embryology,  genetics,  physiology*
Drosophila Proteins / genetics,  physiology*
Gene Targeting
Genes, Insect
Membrane Proteins / genetics,  physiology*
Species Specificity
bcl-2-Associated X Protein / genetics,  physiology
Grant Support
Reg. No./Substance:
0/Bax protein, mouse; 0/DNA Primers; 0/Drosophila Proteins; 0/Membrane Proteins; 0/bcl-2-Associated X Protein; 0/debcl protein, Drosophila

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