| First Author | Sandbrink R | Year | 1994 |
| Journal | J Biol Chem | Volume | 269 |
| Issue | 19 | Pages | 14227-34 |
| PubMed ID | 8188705 | Mgi Jnum | J:18192 |
| Mgi Id | MGI:66205 | Doi | 10.1016/s0021-9258(17)36778-9 |
| Citation | Sandbrink R, et al. (1994) Similar alternative splicing of a non-homologous domain in beta A4-amyloid protein precursor-like proteins. J Biol Chem 269(19):14227-34 |
| abstractText | The beta A4-amyloid protein precursor (APP) is a transmembrane glycoprotein that is the source of the characteristic beta A4-amyloid deposits found in Alzheimer brains. It is expressed in several isoforms generated by alternative splicing of exons 7, 8, and 15, of which the leukocyte-derived APP mRNAs lacking exon 15 are significantly expressed in non-neuronal tissues, but not in neurons. The recent finding of APP-like proteins prompted us to analyze alternative splicing of the nearest relative of APP, the amyloid protein precursor homologue (APPH) or amyloid precursor-like protein 2 (APLP2). We were able to show that there are two alternatively spliced inserts, i.e. the Kunitz protease inhibitor domain and a 12-amino-acid-encoding region on the NH2-terminal side of the transmembrane domain, which is part of the region of highest divergence between APP and APLP2/APPH. Analysis of the tissue-specific differential expression of the resulting four APLP2/APPH mRNA isoforms revealed that isoforms lacking the latter, non-homologous insert are highly expressed in non-neuronal tissues, but only weakly in neurons. While this resembles the tissue-specific alternative splicing of exon 15 of APP, expression of the Kunitz protease inhibitor-encoding exon of APLP2/APPH is abundant in both neuronal and non-neuronal tissues and thus differs from APP. Because of the similar regulation of alternative splicing of exon 15 of APP and the described APLP2/APPH insert, and because of structural similarities of the sequences and the predicted secondary structures, a functional homology of alternatively spliced isoforms of APP and APLP2/APPH is suggested. |
