Reverse Genetic Analysis of Caenorhabditis elegans Presenilins Reveals Redundant but Unequal Roles for sel-12 and hop-1 in Notch-Pathway Signaling

• Published in: Proceedings of the National Academy of Sciences - PNAS 1999-03, Vol.96 (5), p.2497-2502
• Main Authors: Westlund, Bethany, Parry, Dianne, Clover, Ralph, Basson, Michael, Johnson, Carl D.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animals; Antibodies; Biological Sciences; Caenorhabditis elegans; Caenorhabditis elegans - embryology; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins; Embryo, Nonmammalian - physiology; Embryonic Induction; Embryos; Female; Gene Deletion; Genes; Genetic mutation; Genotype; Genotypes; Germ cells; Gonads; Helminth Proteins - genetics; Helminth Proteins - physiology; Humans; Libraries; Membrane Proteins - genetics; Membrane Proteins - physiology; Mice; Mutagenesis; Mutagens; Mutation; Neurology; Phenotype; Phenotypes; Presenilins; Receptors, Notch; Reverse genetics; Signal Transduction - physiology; Ultraviolet Rays; Vulva - abnormalities; Vulva - embryology; Worms
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.5.2497

Mutations in the human presenilin genes PS1 and PS2 cause early-onset Alzheimer's disease. Studies in Caenorhabditis elegans and in mice indicate that one function of presenilin genes is to facilitate Notch-pathway signaling. Notably, mutations in the C. elegans presenilin gene sel-12 reduce signaling through an activated version of the Notch receptor LIN-12. To investigate the function of a second C. elegans presenilin gene hop-1 and to examine possible genetic interactions between hop-1 and sel-12, we used a reverse genetic strategy to isolate deletion alleles of both loci. Animals bearing both hop-1 and sel-12 deletions displayed new phenotypes not observed in animals bearing either single deletion. These new phenotypes--germ-line proliferation defects, maternal-effect embryonic lethality, and somatic gonad defects--resemble those resulting from a reduction in signaling through the C. elegans Notch receptors GLP-1 and LIN-12. Thus SEL-12 and HOP-1 appear to function redundantly in promoting Notch-pathway signaling. Phenotypic analyses of hop-1 and sel-12 single and double mutant animals suggest that sel-12 provides more presenilin function than does hop-1.