Presenilin Function in Caenorhabditis elegansSmialowska A. · Baumeister R.
aBio3/Bioinformatics and Molecular Genetics, and bZBSA/Freiburg Center for Systems Biology, University of Freiburg, Freiburg, Germany
The genome of the nematode Caenorhabditis elegans contains homologs of several genes associated with familial Alzheimer’s disease in humans. apl-1 encodes a transmembrane protein belonging to the amyloid precursor protein family, sel-12 and hop-1 are the two somatically expressed presenilin genes that resemble PS1 and PS2 on both a structural and a functional level. Mutations in the sel-12-encoded presenilin gene cause defective Notch/lin-12 signaling and result in reduced egg-laying, caused by cell specification and cell attachment defects. spr-1, spr-3, spr-4 and spr-5 were identified as the suppressors of the egg-laying defect of presenilin/sel-12 loss of function mutants in genetic suppressor screens. The corresponding proteins are C. elegans homologs of human REST, CoREST and LSD1, respectively. REST/NSRF (Re1 silencing transcription factor/neural-restrictive silencing factor) is a transcriptional repressor that blocks the expression of neuronal genes in non-neuronal tissues in vertebrates. CoREST is a conserved histone deacetylase and demethylase-containing co-repressor complex possessing a potential chromatin-modifying activity. It is recruited to the promoter via REST-mediated DNA binding. LSD1 is a flavin-dependent demethylase of histone H3. Mutations in spr-1, spr-3, spr-4 and spr-5 genes suppress the egg-laying phenotype of sel-12 loss of function mutants by derepressing the expression of the second C. elegans presenilin gene, hop-1.
Ralf Baumeister, PhD
ZBSA/Bioinformatics and Molecular Genetics
DE–79104 Freiburg (Germany)
Tel. +49 761 203 2799, Fax +49 761 203 8351, E-Mail email@example.com
Number of Print Pages : 6
Number of Figures : 4, Number of Tables : 0, Number of References : 23
Vol. 3, No. 4-5, Year 2006 (Cover Date: October 2006)
Journal Editor: Nitsch, R.M. (Zürich)
ISSN: 1660–2854 (print), 1660–2862 (Online)
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