[ trivia ]
Interesting factoid...... Rong Wang, a SIBI collaborator at Rockefeller, was apparently trained in the lab of Sisodia......
J Biol Chem 1991 Sep 5;266(25):16960-16964
Secretion of the beta/A4 amyloid precursor protein. Identification of a
cleavage site in cultured mammalian cells.
Wang R, Meschia JF, Cotter RJ, Sisodia SS
Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2181.
Alzheimer's disease, a progressive neurodegenerative disorder, affects greater than 10% of the population of individuals greater
than 65 years of age. A principal neuropathological feature of this disease is the senile plaque, a fibrillar extracellular deposit
primarily composed of a approximately 4-kDa peptide, beta/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. |
