| Title: | daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway |
| Author(s): | Li W; Kennedy SG; Ruvkun G; |
| Address: | "Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA" |
| ISSN/ISBN: | 0890-9369 (Print) 0890-9369 (Linking) |
| Abstract: | "In Caenorhabditis elegans, the decision to enter a developmentally arrested dauer larval stage is triggered by a combination of signals from sensory neurons in response to environmental cues, which include a dauer pheromone. These sensory inputs are coupled to the parallel DAF-2/insulin receptor-like and DAF-7/TGFbeta-like signaling pathways. Although sensory inputs have been shown to physiologically regulate DAF-7/TGFbeta expression, no such regulation of insulin-like ligands in the DAF-2 pathway has been reported. We show here that daf-28 encodes an insulin-like protein, which when mutated causes dauer arrest and down-regulation of DAF-2/IR signaling. A daf-28GFP fusion gene is expressed in ASI and ASJ, two sensory neurons that regulate dauer arrest. daf-28GFP expression in ASI and ASJ is down-regulated under dauer-inducing conditions and in mutants of DAF-11/guanylyl cyclase, a predicted component of the dauer-pheromone-sensing pathway. Thus, daf-28 expression in sensory neurons is regulated by the environmental cues that normally trigger dauer arrest. Among the 38 C. elegans insulin genes, daf-28 is so far the only insulin mutant to affect dauer arrest. daf-28 was revealed from this functional redundancy by a dominant-negative allele that disrupts a probable proteolytic processing site required for insulin maturation. This DAF-28 mutant is likely to be poisonous to wild-type DAF-28 and other insulins" |
| Keywords: | "Amino Acid Sequence Animals Animals, Genetically Modified Base Sequence Caenorhabditis elegans/*genetics Caenorhabditis elegans Proteins/chemistry/*genetics DNA Primers Environment *Gene Expression Regulation/*physiology Guanylate Cyclase/genetics Insulin;" |
| Notes: | "MedlineLi, Weiqing Kennedy, Scott G Ruvkun, Gary eng R01 AG014161/AG/NIA NIH HHS/ R01 AG016636/AG/NIA NIH HHS/ R01 AG 16636/AG/NIA NIH HHS/ R01 AG 14161/AG/NIA NIH HHS/ Comparative Study Research Support, U.S. Gov't, P.H.S. 2003/03/26 Genes Dev. 2003 Apr 1; 17(7):844-58. doi: 10.1101/gad.1066503. Epub 2003 Mar 21" |
