A ubiquitin ligase complex regulates caspase activation during sperm differentiation in Drosophila

Eli Arama, Maya Bader, Gabrielle E. Rieckhof, Hermann Steller*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

98 Citations (Scopus)

Abstract

In both insects and mammals, spermatids eliminate their bulk cytoplasm as they undergo terminal differentiation. In Drosophila, this process of dramatic cellular remodeling requires apoptotic proteins, including caspases. To gain further insight into the regulation of caspases, we screened a large collection of sterile male flies for mutants that block effector caspase activation at the onset of spermatid individualization. Here, we describe the identification and characterization of a testis-specific, Cullin-3 -dependent ubiquitin ligase complex that is required for caspase activation in spermatids. Mutations in either a testis-specific isoform of Cullin-3 (Cul3(Testis)), the small RING protein Roc1b, or a Drosophila orthologue of the mammalian BTB-Kelch protein Klhl10 all reduce or eliminate effector caspase activation in spermatids. Importantly, all three genes encode proteins that can physically interact to form a ubiquitin ligase complex. Roc1b binds to the catalytic core of Cullin-3, and Klhl10 binds specifically to a unique testis-specific N-terminal Cullin-3 (TeNC) domain of Cul3Testis that is required for activation of effector caspase in spermatids. Finally, the BIR domain region of the giant inhibitor of apoptosis -like protein dBruce is sufficient to bind to Klhl10, which is consistent with the idea that dBruce is a substrate for the Cullin-3-based E3-ligase complex. These findings reveal a novel role of Cullin-based ubiquitin ligases in caspase regulation.

Original languageEnglish
Pages (from-to)2270-2287
Number of pages18
JournalPLoS Biology
Volume5
Issue number10
DOIs
Publication statusPublished - Oct 2007

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry,Genetics and Molecular Biology
  • General Neuroscience
  • General Agricultural and Biological Sciences

Fingerprint

Dive into the research topics of 'A ubiquitin ligase complex regulates caspase activation during sperm differentiation in Drosophila'. Together they form a unique fingerprint.

Cite this