Cleavage at the N-terminal site of Alzheimer amyloid beta/A4 protein is essential for its secretion.
To characterize the secretory pathway of Alzheimer amyloid beta/A4 protein (beta/A4), mutated cDNAs of amyloid precursor protein (APP) were expressed transiently in COS cells. Although the expression of C100 (Met671-Asn770) resulted in the secretion of beta/A4-like peptide, the cells expressing the mutated APPs with the longer N-terminal domain beyond beta/A4 sequence secreted little beta/A4-like peptide. The C-terminal domain truncated APPs, with a stop codon at the end of beta/A4 sequence or the predicted membrane spanning domain produced little beta/A4-like peptide. When beta/A4 was expressed with direct addition of the signal sequence, beta/A4-like peptide was found in the cell lysate but little of it was secreted. Hence, the secretion of beta/A4 was started initially by cleavage at the N-terminal site of beta/A4, although cleavage at its C-terminal site was also necessary for its secretion.
Maruyama
K
K
Laboratory of Neurochemistry, National Institute for Physiological Sciences, Aichi, Japan.
Kawamura
Y
Y
Asada
H
H
Ishiura
S
S
Obata
K
K
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006868:Hydrolysis; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000378:metabolism
D016229:Amyloid beta-Peptides; D021382:Protein Sorting Signals