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...
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| Veröffentlicht in: | Genes & development 2004-09, Vol.18 (17), p.2120-2133 |
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| creator | Ludewig, Andreas H Kober-Eisermann, Corinna Weitzel, Cindy Bethke, Axel Neubert, Kerstin Gerisch, Birgit Hutter, Harald Antebi, Adam |
| description | 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. |
| doi_str_mv | 10.1101/gad.312604 |
| format | Article |
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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.</description><identifier>ISSN: 0890-9369</identifier><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.312604</identifier><identifier>PMID: 15314028</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Aging - genetics ; Amino Acid Sequence ; Animals ; beta-Galactosidase ; Caenorhabditis elegans ; Caenorhabditis elegans - genetics ; Caenorhabditis elegans - physiology ; Caenorhabditis elegans Proteins - metabolism ; Caenorhabditis elegans Proteins - physiology ; DNA, Complementary - genetics ; Electrophoresis, Polyacrylamide Gel ; Gene Components ; Larva - genetics ; Larva - growth & development ; Lipid Metabolism ; Lipids - genetics ; Luciferases ; Molecular Sequence Data ; Phenotype ; Plasmids - genetics ; Protein Isoforms - metabolism ; Protein Isoforms - physiology ; Protein Structure, Tertiary ; Receptors, Cytoplasmic and Nuclear - metabolism ; Receptors, Cytoplasmic and Nuclear - physiology ; Research Papers ; RNA Interference ; Transcription Factors - metabolism ; Transcription Factors - physiology ; Transfection ; Two-Hybrid System Techniques</subject><ispartof>Genes & development, 2004-09, Vol.18 (17), p.2120-2133</ispartof><rights>Copyright © 2004, Cold Spring Harbor Laboratory Press 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-3fd8fc056f1c857b85675b74e876a32e874e8df2bfb40da4ddfc9fa68b8c664b3</citedby><cites>FETCH-LOGICAL-c470t-3fd8fc056f1c857b85675b74e876a32e874e8df2bfb40da4ddfc9fa68b8c664b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC515290/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC515290/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15314028$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ludewig, Andreas H</creatorcontrib><creatorcontrib>Kober-Eisermann, Corinna</creatorcontrib><creatorcontrib>Weitzel, Cindy</creatorcontrib><creatorcontrib>Bethke, Axel</creatorcontrib><creatorcontrib>Neubert, Kerstin</creatorcontrib><creatorcontrib>Gerisch, Birgit</creatorcontrib><creatorcontrib>Hutter, Harald</creatorcontrib><creatorcontrib>Antebi, Adam</creatorcontrib><title>A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>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.</description><subject>Aging - genetics</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>beta-Galactosidase</subject><subject>Caenorhabditis elegans</subject><subject>Caenorhabditis elegans - genetics</subject><subject>Caenorhabditis elegans - physiology</subject><subject>Caenorhabditis elegans Proteins - metabolism</subject><subject>Caenorhabditis elegans Proteins - physiology</subject><subject>DNA, Complementary - genetics</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Gene Components</subject><subject>Larva - genetics</subject><subject>Larva - growth & development</subject><subject>Lipid Metabolism</subject><subject>Lipids - genetics</subject><subject>Luciferases</subject><subject>Molecular Sequence Data</subject><subject>Phenotype</subject><subject>Plasmids - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Protein Isoforms - physiology</subject><subject>Protein Structure, Tertiary</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Receptors, Cytoplasmic and Nuclear - physiology</subject><subject>Research Papers</subject><subject>RNA Interference</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription Factors - physiology</subject><subject>Transfection</subject><subject>Two-Hybrid System Techniques</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAUhS0EokNhww9AXrGomqkdP7NgUY0KVKrEBtaWY9-EIMcOdjKi_x6jGfFYsTpHut-5OtJB6DUle0oJvRmt3zPaSsKfoB0VvGsEV-op2hHdkaZjsrtAL0r5RgiRRMrn6IIKRjlp9Q4ttzimIwQcNxfAZpzBwbKmfONShnELtnrs0rwE-FE1rjmFgg97DAFGGwsO0zJ5PMNq-xSmMl_jYPPRBuyh_k3LDHG9xjZ6bMcpji_Rs8GGAq_Oeom-vL_7fPjYPHz6cH-4fWgcV2Rt2OD14IiQA3VaqF4LqUSvOGglLWurVOuHth96Trzl3g-uG6zUvXZS8p5donenv8vWz-BdbZFtMEueZpsfTbKT-fcSp69mTEcjqGg7UvNvz_mcvm9QVjNPxUEINkLaipFSM87U_0GqSaso0RW8OoEup1IyDL_LUGJ-DWnqkOY0ZIXf_F3_D3pejv0EzT6cfg</recordid><startdate>20040901</startdate><enddate>20040901</enddate><creator>Ludewig, Andreas H</creator><creator>Kober-Eisermann, Corinna</creator><creator>Weitzel, Cindy</creator><creator>Bethke, Axel</creator><creator>Neubert, Kerstin</creator><creator>Gerisch, Birgit</creator><creator>Hutter, Harald</creator><creator>Antebi, Adam</creator><general>Cold Spring Harbor Laboratory Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20040901</creationdate><title>A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging</title><author>Ludewig, Andreas H ; 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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. 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Aging - genetics Amino Acid Sequence Animals beta-Galactosidase Caenorhabditis elegans Caenorhabditis elegans - genetics Caenorhabditis elegans - physiology Caenorhabditis elegans Proteins - metabolism Caenorhabditis elegans Proteins - physiology DNA, Complementary - genetics Electrophoresis, Polyacrylamide Gel Gene Components Larva - genetics Larva - growth & development Lipid Metabolism Lipids - genetics Luciferases Molecular Sequence Data Phenotype Plasmids - genetics Protein Isoforms - metabolism Protein Isoforms - physiology Protein Structure, Tertiary Receptors, Cytoplasmic and Nuclear - metabolism Receptors, Cytoplasmic and Nuclear - physiology Research Papers RNA Interference Transcription Factors - metabolism Transcription Factors - physiology Transfection Two-Hybrid System Techniques |
| title | A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging |
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