Secretion of Alzheimer beta/A4 protein (1-40) and intracellular retention of beta/A4 protein (1-42) in transfected COS cells.
The amyloid beta/A4 protein (beta/A4) of Alzheimer disease is heterogeneous. A beta 1-40 (Asp1 to Val40) is rather soluble, whereas A beta 1-42 (Asp1 to Ala42) is more insoluble and can be the seed of deposition of A beta 1-40. Although beta/A4 itself could not be expressed transiently in COS cells by cDNA transfection, it was expressed after directly adding a signal sequence to its N-terminal end. The expressed A beta 1-40 was secreted, whereas A beta 1-42 was hardly secreted. A beta 1-40 secretion was not inhibited by metabolic inhibitors such as brefeldin A. The normally produced A beta 1-40 could not be retained intracellularly, whereas the abnormally generated A beta 1-42 might be accumulated intracellularly, resulting in cellular toxicity.
Maruyama
K
K
Laboratory of Neurochemistry, National Institute for Physiological Sciences, Aichi, Japan.
Tagawa
K
K
Kawamura
Y
Y
Asada
H
H
Ishiura
S
S
Obata
K
K
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D020126:Brefeldin A; D002460:Cell Line; D017077:Culture Media, Conditioned; D003517:Cyclopentanes / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D008744:Methylamines / Q000494:pharmacology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011480:Protease Inhibitors / Q000494:pharmacology; D021382:Protein Sorting Signals / Q000737:chemistry / Q000235:genetics; D051381:Rats; D013329:Structure-Activity Relationship; D014162:Transfection
D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D003517:Cyclopentanes; D018076:DNA, Complementary; D008744:Methylamines; D011480:Protease Inhibitors; D021382:Protein Sorting Signals; D020126:Brefeldin A; C027451:methylamine