Altered binding of mutated presenilin with cytoskeleton‐interacting proteins

FEBS Letters

Johnston, Jane M.¹  Johnsingh, Amit A.²  Merz, George¹  Xu, Jiliu¹  Jacobsen, J.Steven³  Kotula, Leszek¹  Tezapsidis, Nikolaos² 

[1] NYS Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA;Department of Psychiatry, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1229, New York, NY 10029, USA;Department of CNS Disorders, CN-8000, Wyeth-Ayerst Research, Princeton, NJ 08543, USA

关键词: Alzheimer's disease;    Presenilin;    Mutation;    170 kDa cytoplasmic linker protein;    Restin;    Protein interaction;    aa;    amino acid;    AD;    Alzheimer's disease;    APP;    amyloid precursor protein;    AT;    PS1 N-terminus-directed antibodies;    β-Gal;    β-galactosidase;    BSA;    bovine serum albumin;    CLIP-170;    170 kDa cytoplasmic linker protein;    CT;    PS1 C-terminus-directed antibodies;    DMEM;    Dulbecco's modified essential medium;    EDTA;    ethanyldiamino tetraacidic acid;    ER;    endoplasmic reticulum;    FAD;    familial Alzheimer's disease;    FCS;    fetal calf serum;    GST;    glutathione-S-transferase;    IPTG;    isopropyl β-D-thiogalactopyranoside;    K d;    dissociation constant;    MIP;    microtubule-interacting protein;    MNR2;    peptide corresponding to 311–330 amino acids of PS1;    nt;    nucleotide;    PBS;    phosphate-buffered saline;    PS1;    presenilin 1;    PS2;    presenilin 2;    Restin;    Reed–Sternberg cells of Hodgkin's disease-expressed intermediate filament-associated protein;    SREBP;    sterol regulatory binding protein;    TBS;    Tris-buffered saline;    wt;    wild-type;    Zeo;    zeocin resistance gene;   

DOI  :  10.1016/S0014-5793(99)01664-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Ca²⁺. 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.

【 授权许可】

Unknown