Spindle assembly checkpoint gene mdf-1 regulates germ cell proliferation in response to nutrition signals in C. elegans.
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.
Watanabe
Sonoko
S
Department of Molecular Pharmacology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Yamamoto
Takaharu G
TG
Kitagawa
Risa
R
D000483:Alleles; D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics*; D049109:Cell Proliferation; D005502:Food; D005508:Food Deprivation; D005854:Germ Cells / Q000166:cytology* / Q000201:enzymology; D006579:Heterozygote; D006720:Homozygote; D007814:Larva; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C412839:MDF-1 protein, C elegans; D013912:Threonine; D051057:Proto-Oncogene Proteins c-akt