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A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging

MPS-Authors

Ludewig,  Andreas H.
Max Planck Society;

Kober-Eisermann,  Corinna
Max Planck Society;

Weitzel,  Cindy
Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50099

Bethke,  Axel
Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50442

Neubert,  Kerstin
Bioinformatics (Ralf Herwig), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50166

Gerisch,  Birgit
Ribosomes, Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50070

Antebi,  Adam
Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Ludewig, A. H., Kober-Eisermann, C., Weitzel, C., Bethke, A., Neubert, K., Gerisch, B., et al. (2004). A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging. Genes & Development: A Journal of Celluar and Molecular Biology, 18(17), 2120-2133. doi:10.1101/gad.312604.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-87ED-3
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 TGF{beta} 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.