title: Specificity in recognition of amyloid-beta peptide by the serpin-enzyme complex receptor in hepatoma cells and neuronal cells.
abstract: The serpin-enzyme complex (SEC) receptor was originally identified using a synthetic peptide (peptide 105Y) based on the sequence of a candidate receptor-binding domain of alpha 1-antitrypsin (1-AT) and was subsequently shown to be a receptor on the surface of hepatocytes, monocytes, and neutrophils for recognition of alpha 1-AT-elastase and several other serpin-enzyme complexes (Perlmutter, D. H., Glover, G. I., Rivetna, M., Schasteen, C. S., and Fallon, R.J. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3753-3757). Studies of the minimal requirements for binding to SEC receptor (SEC-R) showed that a pentapeptide FVFLM within the carboxyl-terminal tail of alpha 1-AT was sufficient for binding to SEC-R and interacted with SEC-R in a sequence-specific manner (Joslin, G., Krause, J. E., Hershey, A. D., Adams, S. P., Fallon, R. J., and Perlmutter, D. H. (1991) J. Biol. Chem. 266, 21897-21902). Sequence motifs bearing homology with this pentapeptide domain were found in the amyloid-beta peptide, and amyloid-beta peptide 1-42 was shown to compete for binding to SEC-R on hepatoma cells (Joslin, G., Fallon, R. J., Bullock, J., Adams, S. P., and Perlmutter, D. H. (1991) J. Biol. Chem, 266, 11281-11288). In this study we examined the sequence specificity by which amyloid-beta peptide competes for binding to SEC-R and examined the possibility that SEC-R is expressed in cells of neuronal origin. The results show that amyloid-beta-(25-35) and amyloid-beta-(31-35) compete for binding to SEC-R as effectively as amyloid-beta-(1-39), amyloid-beta-(1-40), and amyloid-beta-(1-42). Amyloid-beta-(1-16) does not compete for binding to SEC-R. There is cross-competition for binding to the same site by 125I-peptide 105Y and amyloid-beta-(25-35) as well as by 125I-Y amyloid-beta-(25-35) and peptide 105Y. By deletions and substitutions within amyloid-beta-(25-35) and generation of chimeric amyloid-beta-alpha 1-AT peptides, amyloid-beta-(31-35) is shown to be critical for binding to the SEC receptor. However, the upstream region, amyloid-beta-(25-30), also contributes to recognition by SEC-R. The SEC-R is present on the surface of a neuronal cell line PC12 as well as that of murine cortical neurons in primary culture, and the specificity of neuronal SEC-R for amyloid-beta peptide is identical to that on hepatoma cells. Finally SEC-R mediates internalization and degradation of amyloid beta-peptide in PC12 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000378:metabolism*; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D015843:Serpins