GCL and CUL3 Control the Switch between Cell Lineages by Mediating Localized Degradation of an RTK

Dev Cell. 2017 Jul 24;42(2):130-142.e7. doi: 10.1016/j.devcel.2017.06.022.


The separation of germline from somatic lineages is fundamental to reproduction and species preservation. Here, we show that Drosophila Germ cell-less (GCL) is a critical component in this process by acting as a switch that turns off a somatic lineage pathway. GCL, a conserved BTB (Broad-complex, Tramtrack, and Bric-a-brac) protein, is a substrate-specific adaptor for Cullin3-RING ubiquitin ligase complex (CRL3GCL). We show that CRL3GCL promotes PGC fate by mediating degradation of Torso, a receptor tyrosine kinase (RTK) and major determinant of somatic cell fate. This mode of RTK degradation does not depend upon receptor activation but is prompted by release of GCL from the nuclear envelope during mitosis. The cell-cycle-dependent change in GCL localization provides spatiotemporal specificity for RTK degradation and sequesters CRL3GCL to prevent it from participating in excessive activities. This precisely orchestrated mechanism of CRL3GCL function and regulation defines cell fate at the single-cell level.

Keywords: CUL3; GCL; RTK; germ cell; germ cell-less; germline; nuclear lamina; protein degradation; receptor tyrosine kinase; ubiquitin.

MeSH terms

  • Animals
  • Cell Lineage*
  • Cell Membrane / metabolism
  • Conserved Sequence
  • Cullin Proteins / metabolism*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / metabolism*
  • Germ Cells / cytology
  • Germ Cells / metabolism
  • HEK293 Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Mitosis
  • Nuclear Envelope / metabolism
  • Nuclear Localization Signals / metabolism
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Oogenesis
  • Protein Domains
  • Proteolysis*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Substrate Specificity
  • Ubiquitination


  • Cul3 protein, Drosophila
  • Cullin Proteins
  • Drosophila Proteins
  • Intercellular Signaling Peptides and Proteins
  • Nuclear Localization Signals
  • Nuclear Proteins
  • gcl protein, Drosophila
  • Receptor Protein-Tyrosine Kinases
  • tor protein, Drosophila