Alzheimer's Disease βA4 Protein Release and Amyloid Precursor Protein Sorting Are Regulated by Alternative Splicing*

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 βA4 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 βA4 relative to p3. This is the first example of alternative splicing regulating polarized trafficking of a secretory protein.

• Publication year

  1996

• Venue

  Journal of Biological Chemistry

• Publication date

  1996-05-31

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.271.22.13208PMID 8662794
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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