Open AccessIncreased expression of beta-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage.
Author(s) -
Albert Y. Hung,
Edward H. Koo,
Christian Haass,
Dennis J. Selkoe
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.20.9439
Subject(s) - amyloid precursor protein , cellular differentiation , microbiology and biotechnology , biology , gene isoform , messenger rna , beta (programming language) , hippocampal formation , gene expression , medicine , endocrinology , chemistry , biochemistry , gene , alzheimer's disease , disease , computer science , programming language
Despite increasing evidence for a pathogenetic role for the beta-amyloid precursor protein (beta APP) in Alzheimer disease, the physiological function of the protein remains unclear. The expression of the neural-specific isoform containing 695 amino acids, beta APP695, is consistent with a role for the protein in neuronal development. In this study, we analyzed the expression of beta APP during the retinoic acid-induced neuronal differentiation of P19 murine embryonal carcinoma cells. Northern blot and RNase protection analyses show a selective increase in beta APP695 expression, concomitant with the morphologic differentiation of P19-derived neurons. Moreover, the time course of increase observed for the beta APP695 mRNA is paralleled by other neuronal-specific transcripts. A similar increase in beta APP695 is observed at the protein level. Furthermore, we show that levels of beta APP695 protein progressively increase during the in vitro differentiation of primary hippocampal neurons. The finding that beta APP695 increases selectively and progressively during neuronal differentiation in two different cell culture systems suggests that this isoform has an important cellular function during this process in the brain. Unlike beta APP in most peripheral cell types, the increased levels of beta APP found in terminally differentiated neuronal cells are not processed in significant amounts by secretory cleavage. Thus, differentiation of neurons is accompanied by increased beta APP695 expression and membrane retention of the protein as intact, full-length molecules that could serve as potential substrates for amyloidogenesis.