RRC ID 4315
Author Watanabe S, Yamamoto TG, Kitagawa R.
Title Spindle assembly checkpoint gene mdf-1 regulates germ cell proliferation in response to nutrition signals in C. elegans.
Journal EMBO J.
Abstract 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.
Volume 27(7)
Pages 1085-96
Published 2008-4-9
DOI 10.1038/emboj.2008.32
PII emboj200832
PMID 18309291
PMC PMC2323251
MeSH Alleles Animals Apoptosis Caenorhabditis elegans / cytology* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cell Cycle Proteins / genetics* Cell Proliferation Food* Food Deprivation 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
IF 11.227
Times Cited 16
C.elegans tm2190