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Evidence that production and release of amyloid beta-protein involves the endocytic pathway
Abstract
Amyloid beta-protein (A beta), the 40-43-amino acid polypeptide that is the principal constituent of senile plaques found in Alzheimer's disease, is constitutively produced and released into medium of cultured cells by an unclear mechanism. In this study, we report that one route of A beta generation involves the internalization of cell surface amyloid precursor protein (beta PP) via the coated pit-mediated endocytic pathway. Radiolabeled A beta can be recovered in medium following selective cell surface radioiodination, indicating that cell surface beta PP is a direct precursor to A beta. In addition, deletion of the cytoplasmic domains of beta PP or depletion of potassium in medium, both of which resulted in reduced beta PP internalization, significantly diminished A beta release. Moreover, pulse-chase experiments after surface radioiodination showed that the kinetics of beta PP secretion and A beta release was different, with the latter occurring at a significantly slower rate. We therefore hypothesize that the internalization of cell surface beta PP via coated pit-mediated endocytosis is one pathway leading to A beta generation and release into medium.
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Under physiological expression levels, β-secretase cleavage of wild-type APP has been localized predominantly to endosomal/lysosomal compartments.
“whereas under physiological expression levels, -secretase cleavage of wild-type APP has been localized predominantly to endosomal/lysosomal compartments (Koo and Squazzo, 1994;Haass et al., 1995;Thinakaran et al., 1996).”
From GGA1 Is Expressed in the Human Brain and Affects the Generation of Amyloid β-Peptide (2006) · cites this paper as Koo and Squazzo, 1994
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Connop, B. P., Thies, R. L., Beyreuther, K., Ida, N., & Reiner, P. B. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.721457.x · Cited by 19
Metadata
- Authors
- Koo, E. H., & Squazzo, S. L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-07
- Volume
- 269
- Issue
- 26
- Pages
- 17386-17389
- ISSN
- 0021-9258
- Cited by
- 829
- References
- 3
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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