In:
Journal of Histochemistry & Cytochemistry, SAGE Publications, Vol. 50, No. 5 ( 2002-05), p. 681-690
Abstract:
It has been suggested that the successive proteolytic events leading to the production of the amyloid-β protein from its precursor may take place at different intracellular locations. Using cultured human leptomeningeal smooth muscle cells and brain pericytes, we modulated the intracellular localization of the amyloid-β precursor protein (APP) to study possible effects on its processing. By using immunofluorescence and immunoelectron microscopy we demonstrated that, under normal conditions, the APP is found in small intracellular vesicles, some of which were characterized as lysosomes. Both the cytokine interferon-γ and the lysosomotropic drug chloroquine, but not the cytokines interleukin (IL)-1, IL-6, or tumor necrosis factor-α (TNF-α), induced an accumulation of APP in newly formed multivesicular body-like organelles. The secretion of the amyloid-β precursor protein was slightly reduced by interferon-γ or chloroquine. Double-labeling and tracer molecule uptake experiments showed that the multivesicular body-like organelles were part of the endocytic pathway. Our findings suggest that the multivesicular body-like organelles function as an intermediate organelle in the intracellular trafficking of the APP. Accumulation of the APP in this organelle is reflected by its reduced secretion from the cell.
Type of Medium:
Online Resource
ISSN:
0022-1554
,
1551-5044
DOI:
10.1177/002215540205000509
Language:
English
Publisher:
SAGE Publications
Publication Date:
2002
detail.hit.zdb_id:
1421306-0
SSG:
12
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