Three novel alternatively spliced isoforms of the human beta-site amyloid precursor protein cleaving enzyme (BACE) and their effect on amyloid beta-peptide production

• Published in: Neuroscience letters Vol. 307; no. 1; pp. 9 - 12
• Main Authors: Tanahashi, Hiroshi, Tabira, Takeshi
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 06.07.2001; Elsevier
• Subjects: Alternative splicing; Alternative Splicing - genetics; Alzheimer Disease - enzymology; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid beta; Amyloid beta-Peptides - biosynthesis; Amyloid beta-Protein Precursor - metabolism; Amyloid Precursor Protein Secretases; Aspartic Acid Endopeptidases - genetics; Aspartic Acid Endopeptidases - metabolism; Aspartic protease; b-Site APP cleaving enzyme; BACE protein; Beta-site amyloid precursor protein cleaving enzyme; Biochemistry and metabolism; Biological and medical sciences; Cells, Cultured - metabolism; Central nervous system; Cloning, Molecular; Endoglycosidase H; Endopeptidases; Frontal Lobe - enzymology; Frontal Lobe - physiopathology; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Glycosylation; Humans; Protease; Protein Isoforms - genetics; Protein Structure, Tertiary - genetics; Transfection; Vertebrates: nervous system and sense organs; Alternative splicing; Amyloid beta; Protease; Endoglycosidase H; Beta-site amyloid precursor protein cleaving enzyme; Aspartic protease; Glycosylation; Alzheimer's disease; Human; Peptidases; Molecular form; Enzyme; Central nervous system; Hydrolases; Molecular cloning; Amyloid precursor protein; Brain (vertebrata)
• DOI: 10.1016/S0304-3940(01)01912-7
• ISSN: 0304-3940

Three novel alternatively spliced transcripts of the beta-site amyloid precursor protein cleaving enzyme (BACE) were cloned from human brain. Alternative splicing of the RNA occurs at an internal donor in exon 3 and/or an internal acceptor in exon 4. The splicing events lead to a deletion of 25 (BACE-I-476), 44 (BACE-I-457) and 69 (BACE-I-432) amino acids and the latter two caused the loss of two of four N-linked glycosylation sites. Although the mature form of BACE-501 was resistant to endoglycosidase H treatment, glycosylated forms of BACE-I-457 and BACE-I-476 were sensitive. This result suggests that BACE-I-457 and BACE-I-476 underwent different post-translational modifications. Moreover, the beta-secretase activity of BACE-I-457 and BACE-I-476 was significantly weaker than that of BACE-501. Thus, these isoforms may contribute to a physiological function of BACE.