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Genetic analysis of Caenorhabditis elega ... ptor interaction or competition
Genetic analysis of Caenorhabditis elegans glp-1 mutants suggests receptor interaction or competition
5384
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.
Pepper AS, Killian DJ, Hubbard EJ
Genetics
2003-01-01 00:00
163
1
115-32
Animals,Caenorhabditis elegans,Caenorhabditis elegans Proteins,DNA-Binding Proteins,Glucagon,Glucagon-Like Peptide 1,Membrane Proteins,Mutation,Peptide Fragments,Protein Precursors,Receptors, Notch,Signal Transduction,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
Department of Biology, New York University, New York, New York 10003, USA.
Genetics
NIGMS GM-61706, NICHD T32HD07520
0016-6731
0
False
12586701
