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| Alzheimer's disease beta A4 protein release and amyloid precursor protein sorting are regulated by alternative splicing |
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| Author(s): Hartmann T, Bergsdorf C, Sandbrink R, Tienari PJ, Multhaup G, Ida N, Bieger S, Dyrks T, Weidemann A, Masters CL, Beyreuther K |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 271 Issue: 22 Pages: 13208-13214 Published: MAY 31 1996 |
| Times Cited: 19 References: 33 |
| Abstract: We show here that alternative splicing influences the polarized secretion of amyloid precursor protein (APP) as well as the release of its proteolytic 3-4-kDa fragments beta A4 and p3. In Madin-Darby canine kidney II cells stably transfected with various APP isoforms and APP mutants, APPsec was consistently secreted basolaterally. In contrast, Madin-Darby canine kidney II cells transfected with L-APP677, which occurs naturally by alternative splicing of exon 15, secreted this isoform both apically and basolaterally, while maintaining the basolateral sorting of endogenous APPsec. This suggests that the alternative splicing of APP exon 15 modulates the polarized sorting of secretory APP. The same alternative splicing event also decreased the production of beta A4 relative to p3. This is the first example of alternative splicing regulating polarized trafficking of a secretory protein. |
| Document Type: Article |
| Language: English |
| Reprint Address: Hartmann, T (reprint author), UNIV HEIDELBERG, ZENTRUM MOLEK BIOL, INF 282, D-69120 HEIDELBERG, GERMANY |
Addresses:
1. UNIV HEIDELBERG, DEPT ANAT & CELL BIOL, D-69120 HEIDELBERG, GERMANY
2. SCHERING AG, D-13353 BERLIN, GERMANY
3. UNIV MELBOURNE, DEPT PATHOL, MELBOURNE, VIC 3052 AUSTRALIA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: UN474 |
| ISSN: 0021-9258 |
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