hide
Free keywords:
Aging/*genetics
Amino Acid Sequence
Animals
Caenorhabditis elegans/*genetics/physiology
Caenorhabditis elegans Proteins/metabolism/*physiology
DNA, Complementary/genetics
Electrophoresis, Polyacrylamide Gel
Gene Components
Larva/genetics/growth & development
*Lipid Metabolism
Lipids/genetics
Luciferases
Molecular Sequence Data
*Phenotype
Plasmids/genetics
Protein Isoforms/metabolism/physiology
Protein Structure, Tertiary
RNA Interference
Receptors, Cytoplasmic and Nuclear/metabolism/*physiology
Transcription Factors/metabolism/*physiology
Transfection
Two-Hybrid System Techniques
beta-Galactosidase
Abstract:
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.
