Secretion of the β/A4 amyloid precursor protein: Identification of a cleavage site in cultured mammalian cells

R. Wang, J. F. Meschia, R. J. Cotter, S. S. Sisodia

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

Alzheimer's disease, a progressive neurodegenerative disorder, affects > 10% of the population of individuals >65 years of age. A principal neuropathological feature of this disease is the senile plaque, a fibrillar extracellular deposit primarily composed of a ~4-kDa peptide, β/A4, derived from the amyloid precursor protein (APP). Studies in cultured cells have documented that APP matures through a constitutive secretory pathway and is cleaved at or near the cell surface to release a large ectodomain into the extracellular space. To define the APP cleavage site, we constructed a Chinese hamster ovary cell line, which constitutively overexpresses human APP-770, and analyzed the COOH termini of secreted APP-770-related molecules. Using plasma desorption mass spectrometry and chemical microsequencing, we document that an APP cleavage site in Chinese hamster ovary cells leading to secretion occurs immediately COOH-terminal to lysine residue 687, which lies adjacent to the hydrophobic membrane-spanning domain.

Original languageEnglish (US)
Pages (from-to)16960-16964
Number of pages5
JournalJournal of Biological Chemistry
Volume266
Issue number25
StatePublished - Nov 1 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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