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Altered binding of mutated presenilin with cytoskeleton‐interacting proteins 1
Author(s) -
Johnsingh Amit A.,
Johnston Jane M.,
Merz George,
Xu Jiliu,
Kotula Leszek,
Jacobsen J.Steven,
Tezapsidis Nikolaos
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01664-6
Subject(s) - cytoplasm , presenilin , ionomycin , microbiology and biotechnology , cytoskeleton , biology , transfection , mutant , thapsigargin , gene , endoplasmic reticulum , genetics , intracellular , cell , alzheimer's disease , medicine , disease , pathology
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.