Abstract
The majority of familial Alzheimer's disease (AD) cases are linked to mutations on presenilin 1 and 2 genes (PS1 and PS2). The normal function of the proteins and the mechanisms underlying early-onset AD are currently unknown. To address this, we screened an expression library for proteins that bind differentially to the wild-type PS1 and mutant in the large cytoplasmic loop (PS1L). Thus we isolated the C-terminal tail of the 170 kDa cytoplasmic linker protein (CLIP-170) and Reed-Sternberg cells of Hodgkin's disease-expressed intermediate filament-associated protein (Restin), cytoplasmic proteins linking vesicles to the cytoskeleton. PS1L binding to CLIP-170/restin requires Ca(2+). Treating cells with thapsigargin or ionomycin increased the mutated PS1 in CLIP-170 immunoprecipitates. Further, PS1 and CLIP-170 co-localize in transfected cells and neuronal cultures.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alzheimer Disease / metabolism
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Conserved Sequence
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Cytoskeleton / metabolism*
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Humans
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Intermediate Filament Proteins / chemistry*
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Intermediate Filament Proteins / genetics
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Intermediate Filament Proteins / isolation & purification
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Ionomycin / pharmacology
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Microtubule-Associated Proteins / chemistry*
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / isolation & purification
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Mutation
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Neoplasm Proteins / chemistry*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / isolation & purification
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Peptide Library
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Precipitin Tests
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Presenilin-1
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Reed-Sternberg Cells / metabolism
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Thapsigargin / pharmacology
Substances
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Intermediate Filament Proteins
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Membrane Proteins
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Microtubule-Associated Proteins
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Neoplasm Proteins
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PSEN1 protein, human
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Peptide Library
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Presenilin-1
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cytoplasmic linker protein 170
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Ionomycin
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Thapsigargin