Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling

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 signali...

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Main Authors: Westlund, Bethany, Parry, Dianne, Clover, Ralph, Basson, Michael, Johnson, Carl D.
Formato: Artigo
Idioma:en
Publicado em: The National Academy of Sciences 1999
Assuntos:
Biological Sciences
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC26813/
https://ncbi.nlm.nih.gov/pubmed/10051671
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spelling pubmed-268132001-03-17 Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling Westlund, Bethany Parry, Dianne Clover, Ralph Basson, Michael Johnson, Carl D. Proc Natl Acad Sci U S A Biological Sciences 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. The National Academy of Sciences 1999-03-02 /pmc/articles/PMC26813/ /pubmed/10051671 Text en Copyright © 1999, The National Academy of Sciences
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Biological Sciences
spellingShingle Biological Sciences
Westlund, Bethany
Parry, Dianne
Clover, Ralph
Basson, Michael
Johnson, Carl D.
Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling
description 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.
author Westlund, Bethany
Parry, Dianne
Clover, Ralph
Basson, Michael
Johnson, Carl D.
author_facet Westlund, Bethany
Parry, Dianne
Clover, Ralph
Basson, Michael
Johnson, Carl D.
author_sort Westlund, Bethany
title Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling
title_short Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling
title_full Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling
title_fullStr Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling
title_full_unstemmed Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling
title_sort reverse genetic analysis of caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in notch-pathway signaling
publisher The National Academy of Sciences
publisher_facet The National Academy of Sciences
publishDate 1999
url https://ncbi.nlm.nih.gov/pmc/articles/PMC26813/
https://ncbi.nlm.nih.gov/pubmed/10051671
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