Secretion of long Abeta-related peptides processed at epsilon-cleavage site is dependent on the alpha-secretase pre-cutting.
Abeta is the major component of amyloid in the brain in Alzheimer's disease and is derived from Alzheimer amyloid precursor protein (APP) by sequential proteolytic cleavage involving alpha-, beta- and gamma-secretase. Recently, gamma-secretase was shown to cleave near the cytoplasmic membrane boundary of APP (called the epsilon-cleavage), as well as in the middle of the membrane domain (gamma-cleavage). However, the precise relationship between gamma- and epsilon-cleavage is still unknown. In this paper, I analyzed Abeta-related peptides using immunoprecipitation and liquid chromatography ion trap mass spectrometer and found some long Abeta-related peptides, starting at Abeta residues 16Lys-23Asp and ending at 43Thr-52Leu, in the culture media of COS-1 cells and in human brain extract. These results indicated that longer Abeta-related peptides cleaved at epsilon-cleavage site were secreted under normal conditions and were dependent on the alpha-secretase cleavage products.
Kametani
Fuyuki
F
Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagayaku, Tokyo 156-8585, Japan. kametani@prit.go.jp
D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary
D016229:Amyloid beta-Peptides; D010455:Peptides; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human