Secretion of the β/A4 amyloid precursor protein

Identification of a cleavage site in cultured mammalian cells

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

Research output: Contribution to journalArticle

141 Citations (Scopus)

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 - 1991
Externally publishedYes

Fingerprint

Amyloid beta-Protein Precursor
Cultured Cells
Cells
Cricetulus
Ovary
Secretory Pathway
Amyloid Plaques
Extracellular Space
Neurodegenerative Diseases
Lysine
Mass spectrometry
Desorption
Mass Spectrometry
Alzheimer Disease
Deposits
Membranes
Plasmas
Cell Line
Peptides
Molecules

ASJC Scopus subject areas

  • Biochemistry

Cite this

Secretion of the β/A4 amyloid precursor protein : Identification of a cleavage site in cultured mammalian cells. / Wang, R.; Meschia, James F; Cotter, R. J.; Sisodia, S. S.

In: Journal of Biological Chemistry, Vol. 266, No. 25, 1991, p. 16960-16964.

Research output: Contribution to journalArticle

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