Genetic analysis of Caenorhabditis elegans glp-1 mutants suggests receptor interaction or competition

Genetics. 2003 Jan;163(1):115-32. doi: 10.1093/genetics/163.1.115.


glp-1 encodes a member of the highly conserved LIN-12/Notch family of receptors that mediates the mitosis/meiosis decision in the C. elegans germline. We have characterized three mutations that represent a new genetic and phenotypic class of glp-1 mutants, glp-1(Pro). The glp-1(Pro) mutants display gain-of-function germline pattern defects, most notably a proximal proliferation (Pro) phenotype. Each of three glp-1(Pro) alleles encodes a single amino acid change in the extracellular part of the receptor: two in the LIN-12/Notch repeats (LNRs) and one between the LNRs and the transmembrane domain. Unlike other previously described gain-of-function mutations that affect this region of LIN-12/Notch family receptors, the genetic behavior of glp-1(Pro) alleles is not consistent with simple hypermorphic activity. Instead, the mutant phenotype is suppressed by wild-type doses of glp-1. Moreover, a trans-heterozygous combination of two highly penetrant glp-1(Pro) mutations is mutually suppressing. These results lend support to a model for a higher-order receptor complex and/or competition among receptor proteins for limiting factors that are required for proper regulation of receptor activity. Double-mutant analysis with suppressors and enhancers of lin-12 and glp-1 further suggests that the functional defect in glp-1(Pro) mutants occurs prior to or at the level of ligand interaction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism
  • DNA-Binding Proteins / metabolism
  • Glucagon / genetics*
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1
  • Membrane Proteins / metabolism
  • Mutation
  • Peptide Fragments / genetics*
  • Peptide Fragments / metabolism
  • Protein Precursors / genetics*
  • Protein Precursors / metabolism
  • Receptors, Notch
  • Signal Transduction / physiology


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • LAG-1 protein, C elegans
  • Lin-12 protein, C elegans
  • Membrane Proteins
  • Peptide Fragments
  • Protein Precursors
  • Receptors, Notch
  • lag-2 protein, C elegans
  • Glucagon-Like Peptide 1
  • Glucagon