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Originally published as Genetics Published Articles Ahead of Print on September 12, 2005.
Genetics, Vol. 171, 1605-1615, December 2005, Copyright © 2005
doi:10.1534/genetics.105.048041
New Positive Regulators of lin-12 Activity in Caenorhabditis elegans Include the BRE-5/Brainiac Glycosphingolipid Biosynthesis Enzyme
Iskra Katic*,
,
Laura G. Vallier,
,1 and
Iva Greenwald,,2
* Department of Genetics and Development, Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032
2 Corresponding author: 701 W. 168th St., Room 720, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
E-mail: greenwald{at}cancercenter.columbia.edu
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.
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