New positive regulators of lin-12 activity in Caenorhabditis elegans include the BRE-5/Brainiac glycosphingolipid biosynthesis enzyme.
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.
Katic
Iskra
I
Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, 701 W. 168th Street, New York, NY 10032, USA.
Vallier
Laura G
LG
Greenwald
Iva
I
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002874:Chromosome Mapping; D017931:DNA Primers; D005700:Galactosyltransferases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D005816:Genetic Complementation Test; D006028:Glycosphingolipids / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D034622:RNA Interference; D051880:Receptors, Notch; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013489:Suppression, Genetic / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D006028:Glycosphingolipids; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; D051880:Receptors, Notch; C433229:BRE-5 protein, C elegans; D005700:Galactosyltransferases