Genetic analysis of Caenorhabditis elegans glp-1 mutants suggests receptor interaction or competition.
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
Anita S-R
AS
Department of Biology, New York University, New York, New York 10003, USA.
Killian
Darrell J
DJ
Hubbard
E Jane Albert
EJ
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005934:Glucagon / Q000235:genetics* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C099355:LAG-1 protein, C elegans; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D051880:Receptors, Notch; C086488:lag-2 protein, C elegans; D052216:Glucagon-Like Peptide 1; D005934:Glucagon