daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway.
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.
Li
Weiqing
W
Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Kennedy
Scott G
SG
Ruvkun
Gary
G
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics*; D017931:DNA Primers; D004777:Environment; D005786:Gene Expression Regulation / Q000502:physiology*; D006162:Guanylate Cyclase / Q000235:genetics; D007328:Insulin / Q000737:chemistry / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000235:genetics; D061385:Insulins; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D011972:Receptor, Insulin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D007328:Insulin; D061385:Insulins; C473608:daf-28 protein, C elegans; D007334:Insulin-Like Growth Factor I; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D006162:Guanylate Cyclase