A novel F-box protein is required for caspase activation during cellular remodeling in Drosophila

Development. 2010 May;137(10):1679-88. doi: 10.1242/dev.050088. Epub 2010 Apr 14.

Abstract

Terminal differentiation of male germ cells in Drosophila and mammals requires extensive cytoarchitectural remodeling, the elimination of many organelles, and a large reduction in cell volume. The associated process, termed spermatid individualization, is facilitated by the apoptotic machinery, including caspases, but does not result in cell death. From a screen for genes defective in caspase activation in this system, we isolated a novel F-box protein, which we termed Nutcracker, that is strictly required for caspase activation and sperm differentiation. Nutcracker interacts through its F-box domain with members of a Cullin-1-based ubiquitin ligase complex (SCF): Cullin-1 and SkpA. This ubiquitin ligase does not regulate the stability of the caspase inhibitors DIAP1 and DIAP2, but physically binds Bruce, a BIR-containing giant protein involved in apoptosis regulation. Furthermore, nutcracker mutants disrupt proteasome activity without affecting their distribution. These findings define a new SCF complex required for caspase activation during sperm differentiation and highlight the role of regulated proteolysis during this process.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Caspases / metabolism*
  • Cell Differentiation / genetics*
  • Cell Differentiation / physiology
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Enzyme Activation / genetics
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism
  • F-Box Proteins / physiology*
  • Infertility, Male / genetics
  • Infertility, Male / metabolism
  • Male
  • Models, Biological
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Spermatozoa / metabolism
  • Spermatozoa / physiology*
  • Spermatozoa / ultrastructure
  • Testis / metabolism
  • Testis / physiology

Substances

  • Drosophila Proteins
  • F-Box Proteins
  • ntc protein, Drosophila
  • Caspases