Blocking the cleavage at midportion between gamma- and epsilon-sites remarkably suppresses the generation of amyloid beta-protein

Toru Sato; Yu Tanimura; Naoko Hirotani; Takaomi C Saido; Maho Morishima-Kawashima; Yasuo Ihara

doi:10.1016/j.febslet.2005.04.037

Blocking the cleavage at midportion between gamma- and epsilon-sites remarkably suppresses the generation of amyloid beta-protein

FEBS Lett. 2005 May 23;579(13):2907-12. doi: 10.1016/j.febslet.2005.04.037.

Authors

Toru Sato¹, Yu Tanimura, Naoko Hirotani, Takaomi C Saido, Maho Morishima-Kawashima, Yasuo Ihara

Affiliation

¹ Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.

PMID: 15890346
DOI: 10.1016/j.febslet.2005.04.037

Abstract

To examine how gamma- and epsilon-cleavages of beta-amyloid precursor protein (APP) are related, each cleavage site was replaced with a stretch of Trp that cannot be cleaved by gamma-secretase. Replacement of the gamma- or epsilon-site significantly suppressed secretion of amyloid beta-protein (Abeta), and produced longer Abeta or longer APP intracellular domain, respectively. This cleavage at the midportion between gamma- and epsilon-sites was also gamma-secretase-dependent. Blocking this cleavage with a Trp stretch remarkably suppressed Abeta generation, indicating that the midportion cleavage is required for the generation of Abeta.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Amyloid beta-Peptides / biosynthesis*
Amyloid beta-Peptides / chemistry
Amyloid beta-Peptides / metabolism
Animals
CHO Cells
Cricetinae
Culture Media, Conditioned
Hydrolysis
Molecular Sequence Data
Sequence Homology, Amino Acid

Substances

Amyloid beta-Peptides
Culture Media, Conditioned