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P4–070: Amyloid precursor–like proteins 1 and 2 influence proteolytic processing of the amyloid precursor protein by alpha– and beta–secretase
Author(s) -
Neumann Stephanie,
Schöbel Susanne,
Jäger Sebastian,
Haass Christian,
Pietrzik Claus U.,
Lichtenthaler Stefan F.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1808
Subject(s) - alpha secretase , amyloid precursor protein , ectodomain , endocytosis , endosome , amyloid precursor protein secretase , microbiology and biotechnology , endocytic cycle , proteases , internalization , chemistry , p3 peptide , signal transducing adaptor protein , biochemistry , biology , signal transduction , receptor , intracellular , enzyme , alzheimer's disease , medicine , disease , pathology
uptake system in TR-BBB cells, an immortalized cell line derived from brain capillary endothelial cells of temperature-sensitive large T antigen transgenic rat, that recapitulates many of the characteristics of BBB. Results: TR-BBB cells showed a rapid internalization of [125I]-A 1-40, which is saturated at 10 min. Pulse-chase analysis demonstrated that A , once internalized, is rapidly effluxed into the culture media, suggesting that A receptor can be recycled onto the plasma membrane. This uptake was temperature-sensitive and blocked by excess amounts of unlabeled A 1-40 or A 1-42 in a concentration-dependent fashion. These data indicated that TR-BBB cells internalize A by a receptor-mediated mechanism and that A 1-40 and A 1-42 share the same receptor. We also found that receptorassociated protein (RAP), an antagonist of LDL receptor family proteins, significantly inhibits the binding and uptake of A in TR-BBB cells by 80%. We also found that apolipoprotein E (apoE) also inhibited the uptake of A . However, both MEF-1 cells (expressing LRP1 endogenously) and PEA13 cells (LRP1 homozygous deficient) did not internalize A . An in vitro binding assay using immobilized LRP1 also suggested that LRP1 does not directly bind A . Conclusions: These data indicated that a RAP-sensitive, certain LDL receptor family member mediates A uptake in TR-BBB cells, although it still remains possible that LRP1 indirectly mediates the uptake of A through an as yet unknown co-receptor system.