daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway

Genes Dev. 2003 Apr 1;17(7):844-58. doi: 10.1101/gad.1066503. Epub 2003 Mar 21.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics*
  • DNA Primers
  • Environment
  • Gene Expression Regulation* / physiology*
  • Guanylate Cyclase / genetics
  • Insulin / chemistry
  • Insulin / genetics*
  • Insulin-Like Growth Factor I / chemistry
  • Insulin-Like Growth Factor I / genetics
  • Insulins
  • Molecular Sequence Data
  • Neurons, Afferent / physiology
  • Polymorphism, Single Nucleotide*
  • Receptor, Insulin / chemistry
  • Receptor, Insulin / genetics*
  • Receptor, Insulin / physiology*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction / genetics*

Substances

  • Caenorhabditis elegans Proteins
  • DNA Primers
  • Insulin
  • Insulins
  • daf-28 protein, C elegans
  • Insulin-Like Growth Factor I
  • DAF-2 protein, C elegans
  • Receptor, Insulin
  • Guanylate Cyclase