In:
Journal of Cell Science, The Company of Biologists, Vol. 109, No. 5 ( 1996-05-01), p. 991-998
Abstract:
Amyloid βprotein, the principal constituent of amyloid fibrils found in senile plaques and blood vessels in Alzheimer’s disease, is constitutively produced and released into medium of cultured cells. Amyloid βprotein is derived by proteolysis of the βamyloid precursor protein by unclear mechanisms. βamyloid precursor protein is a transmembrane protein which can be processed to release a large secretory product or processed in the endosomal/lysosomal pathway without secretion. Previous studies have shown that from the cell surface, βamyloid precursor protein may be released after cleavage or internalized without cleavage, the latter in a pathway that both produces amyloid βprotein and also targets some molecules to the lysosomal compartment. Analysis of βamyloid precursor protein trafficking is confounded by the concomitant secretion and internalization of molecules from the cell surface. To address this issue, we developed an assay, based on the binding of a radioiodinated monoclonal antibody, to measure the release and internalization of cell surface βamyloid precursor protein in transfected cells. With this approach, we showed that surface βamyloid precursor protein is either rapidly released or internalized, such that the duration at the cell surface is very short. Approximately 30% of cell surface βamyloid precursor protein molecules are released. Following internalization, a fraction of molecules are recycled while the majority of molecules are rapidly sorted to the lysosomal compartment for degradation. When the C terminus of βamyloid precursor protein is deleted, secretion is increased by approximately 2.5-fold as compared to wildtype molecules. There is a concomitant decrease in internalization in these mutant molecules as well as prolongation of the resident time on the cell surface. This observation is consistent with recent evidence that signals within the cytoplasmic domain mediate βamyloid precursor protein internalization.
Type of Medium:
Online Resource
ISSN:
0021-9533
,
1477-9137
DOI:
10.1242/jcs.109.5.991
Language:
English
Publisher:
The Company of Biologists
Publication Date:
1996
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
