The Discovery And Role Of Cd147 As A Subunit Of Gamma-Secretase Complex

gamma-Secretase is a membrane protein complex with unusual aspartyl protease activity that cleaves a variety of type I transmembrane proteins, such as APP Notch and E-cadherin, within their transmembranous regions. gamma-Secretase was first recognized because of its role in the production of A beta peptides that are pathogenic in Alzheimer's disease. There is overwhelming evidence demonstrating that four components, presenilin, nicastrin, APH-1 and PEN-2, are necessary and sufficient for gamma-secretase activity. However, based on the findings of studies conducted on cells overexpressing these four components, the existence of regulatory components of the gamma-secretase complex has been postulated. Recently, an additional subunit of the gamma-secretase complex, membrane protein CD147, has been identified through the purification and characterization of endogenous complexes from HeLa cell membranes. Removal of CD147 from gamma-secretase complexes increases the production of A beta-peptides. Elucidating the molecular mechanism by which CD147 exerts its effect on the activity of the gamma-secretase complex will help us to further understand the pathogenesis of Alzheimer's disease, and may allow for the development of novel therapeutics. (c) 2006 Prous Science. All rights reserved.