Abstract
The presenilin proteins are involved in the proteolytic processing of transmembrane proteins such as Notch/lin-12 and the beta-amyloid precursor protein (betaAPP). Mutation of a conserved cysteine (Cys60Ser) in the C. elegans presenilin sel-12 has a loss-of-function effect on Notch/lin-12 processing similar to that of null mutations in sel-12. In contrast, in mammalian cells, most missense mutations increase gamma-secretase cleavage of betaAPP. We report here that mutation of this conserved cysteine (Cys92Ser) in human presenilin 1 confers a loss-of-function effect in C. elegans, but causes increased A beta42 secretion in mammalian cells. These data suggest that the role of presenilins in Notch/lin-12 signalling and betaAPP processing are either separately regulated activities or independent activities of the presenilins.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid beta-Peptides / genetics*
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Amyloid beta-Peptides / metabolism
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Animals
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins*
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Cysteine / genetics*
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Helminth Proteins / genetics
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Helminth Proteins / metabolism*
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Humans
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism*
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Mutation, Missense / physiology
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Peptide Fragments / genetics*
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Peptide Fragments / metabolism
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Point Mutation / genetics
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Presenilin-1
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Protein Structure, Tertiary / genetics
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Receptors, Notch
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Signal Transduction / genetics
Substances
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Amyloid beta-Peptides
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Caenorhabditis elegans Proteins
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Helminth Proteins
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Lin-12 protein, C elegans
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Membrane Proteins
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PSEN1 protein, human
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Peptide Fragments
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Presenilin-1
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Receptors, Notch
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amyloid beta-protein (1-42)
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Cysteine