New positive regulators of lin-12 activity in Caenorhabditis elegans include the BRE-5/Brainiac glycosphingolipid biosynthesis enzyme

Genetics. 2005 Dec;171(4):1605-15. doi: 10.1534/genetics.105.048041. Epub 2005 Sep 12.


Screens for suppressors of lin-12 hypermorphic alleles in C. elegans have identified core components and modulators of the LIN-12/Notch signaling pathway. Here we describe the recovery of alleles of six new genes from a screen for suppressors of the egg-laying defect associated with elevated lin-12 activity. The molecular identification of one of the new suppressor genes revealed it as bre-5, which had previously been identified in screens for mutations that confer resistance to Bt toxin in C. elegans. bre-5 is the homolog of D. melanogaster brainiac. BRE-5/Brainiac catalyzes a step in the synthesis of glycosphingolipids, components of lipid rafts that are thought to act as platforms for association among certain kinds of membrane-bound proteins. Reducing the activity of several other genes involved in glycosphingolipid biosynthesis also suppresses the effects of constitutive lin-12 activity. Genetic analysis and cell ablation experiments suggest that bre-5 functions prior to ligand-induced ectodomain shedding that activates LIN-12 for signal transduction.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism*
  • Chromosome Mapping
  • DNA Primers
  • Galactosyltransferases / metabolism*
  • Gene Expression Regulation / genetics*
  • Genetic Complementation Test
  • Glycosphingolipids / biosynthesis*
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation / genetics
  • RNA Interference
  • Receptors, Notch
  • Sequence Analysis, DNA
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Suppression, Genetic / genetics*


  • Caenorhabditis elegans Proteins
  • DNA Primers
  • Glycosphingolipids
  • Lin-12 protein, C elegans
  • Membrane Proteins
  • Receptors, Notch
  • BRE-5 protein, C elegans
  • Galactosyltransferases