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BRI2 Interacts with Amyloid Precursor Protein (APP) and Regulates Amyloid β (Aβ) Production.

Authors :
Fotinopoulou, Angeliki
Tsachaki, Maria
Vlavaki, Maria
Poulopoulost, Alexandros
Rostagno, Agueda
Frangione, Bias
Ghiso, Jorge
Efthimiopoulos, Spiros
Source :
Journal of Biological Chemistry. 9/2/2005, Vol. 280 Issue 35, p30768-30772. 5p. 3 Black and White Photographs.
Publication Year :
2005

Abstract

Transmembrane proteins BRI2 and amyloid precursor protein (APP) co-localize with amyloid β (Aβ) lesions in sporadic Alzheimer disease and mutations in both precursor proteins are linked to early-onset familial cases of cerebral amyloidosis associated with dementia and/or cerebral hemorrhage. A specific interaction between BRI2 and APP was unveiled by immunoprecipitation experiments using transfected and non-transfected cells. The use of deletion mutants further revealed that stretches 648–719 of APP751 and 46–106 of BRI2, both inclusive of the full transmembrane domains, are sufficient for the interaction. Removal of most of the APP and BRI2 extracellular domains without affecting the interaction implies that both proteins interact when are expressed on the same cell membrane (cis) rather than on adjacent cells (trans). The presence of BRI2 had a modulatory effect on APP processing, specifically increasing the levels of cellular APP as well as β-secretase-generated COOH-terminal fragments while decreasing the levels of a-secretase-generated COOH-terminal fragments as well as the secretion of total APP and Aβ peptides. Determining the precise molecular pathways affected by the specific binding between APP and BRI2 could result in the identification of common therapeutic targets for these sporadic and familial neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219258
Volume :
280
Issue :
35
Database :
Academic Search Index
Journal :
Journal of Biological Chemistry
Publication Type :
Academic Journal
Accession number :
18352886
Full Text :
https://doi.org/10.1074/jbc.C500231200