Altered binding of mutated presenilin with cytoskeleton-interacting proteins |
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Authors: | Johnsingh A A Johnston J M Merz G Xu J Kotula L Jacobsen J S Tezapsidis N |
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Affiliation: | Department of Psychiatry, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1229, New York, NY 10029, USA. |
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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. |
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