A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging.
Environmental cues transduced by an endocrine network converge on Caenorhabditis elegans nuclear receptor DAF-12 to mediate arrest at dauer diapause or continuous larval development. In adults, DAF-12 selects long-lived or short-lived modes. How these organismal choices are molecularly specified is unknown. Here we show that coregulator DIN-1 and DAF-12 physically and genetically interact to instruct organismal fates. Homologous to human corepressor SHARP, DIN-1 comes in long (L) and short (S) isoforms, which are nuclear localized but have distinct functions. DIN-1L has embryonic and larval developmental roles. DIN-1S, along with DAF-12, regulates lipid metabolism, larval stage-specific programs, diapause, and longevity. Epistasis experiments reveal that din-1S acts in the dauer pathways downstream of lipophilic hormone, insulin/IGF, and TGFbeta signaling, the same point as daf-12. We propose that the DIN-1S/DAF-12 complex serves as a molecular switch that implements slow life history alternatives in response to diminished hormonal signals.
MPI fuer molekulare Genetik, 14195 Berlin, Germany.
Andreas H
AH
Ludewig
Corinna
C
Kober-Eisermann
Cindy
C
Weitzel
Axel
A
Bethke
Kerstin
K
Neubert
Birgit
B
Gerisch
Harald
H
Hutter
Adam
A
Antebi
D000375:Aging / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D040461:Gene Components; D007814:Larva / Q000235:genetics / Q000254:growth & development; D050356:Lipid Metabolism; D008055:Lipids / Q000235:genetics; D008156:Luciferases; D008969:Molecular Sequence Data; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D020798:Two-Hybrid System Techniques; D001616:beta-Galactosidase
D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; D018076:DNA, Complementary; C492744:Din-1 protein, C elegans; D008055:Lipids; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D008156:Luciferases; D001616:beta-Galactosidase