Spindle assembly checkpoint gene mdf-1 regulates germ cell proliferation in response to nutrition signals in C. elegans

EMBO J. 2008 Apr 9;27(7):1085-96. doi: 10.1038/emboj.2008.32. Epub 2008 Feb 28.


When newly hatched Caenorhabditis elegans larvae are starved, their primordial germ cells (PGCs) arrest in the post-S phase. This starvation-induced PGC arrest is mediated by the DAF-18/PTEN-AKT-1/PKB nutrient-sensing pathway. Here, we report that the conserved spindle assembly checkpoint (SAC) component MDF-1/MAD1 is required for the PGC arrest. We identified 2 Akt kinase phosphorylation sites on MDF-1. Expression of a non-phosphorylatable mutant MDF-1 partially suppressed the defect in the starvation-induced PGC arrest in L1 larvae lacking DAF-18, suggesting that MDF-1 regulates germ cell proliferation as a downstream target of AKT-1, thereby demonstrating a functional link between cell-cycle regulation by the SAC components and nutrient sensing by DAF-18-AKT-1 during post-embryonic development. The phosphorylation status of MDF-1 affects its binding to another SAC component, MDF-2/MAD2. The loss of MDF-2 or another SAC component also caused inappropriate germ cell proliferation, but the defect was less severe than that caused by mdf-1 hemizygosity, suggesting that MDF-1 causes the PGC arrest by two mechanisms, one involving MDF-2 and another that is independent of other SAC components.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Apoptosis
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Cycle Proteins / genetics*
  • Cell Proliferation
  • Food Deprivation
  • Food*
  • Germ Cells / cytology*
  • Germ Cells / enzymology
  • Heterozygote
  • Homozygote
  • Larva
  • Models, Biological
  • Mutation / genetics
  • Phosphorylation
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • Spindle Apparatus / metabolism*
  • Threonine / metabolism


  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • MDF-1 protein, C elegans
  • Threonine
  • Proto-Oncogene Proteins c-akt