Nicastrin is dispensable for gamma-secretase protease activity in the presence of specific presenilin mutations.

ABSTRACT: gamma-Secretase is a multisubunit membrane protein complex consisting of presenilin (PS1), nicastrin (NCT), anterior pharynx-1, and presenilin enhancer 2. To analyze the activity of familial Alzheimer disease mutants and to understand the roles of the subunits, we established a yeast transcriptional activator Gal4p system with artificial gamma-secretase substrates containing amyloid precursor protein or Notch fragments. The gamma-secretase activities were evaluated by transcriptional activation of reporter genes upon Gal4p release from the membrane-bound substrates, i.e. growth of yeast on histidine and adenine, or beta-galactosidase assay. We screened and evaluated gamma-secretase mutants using this reconstitution system in yeast, which does not possess endogenous gamma-secretase activity

SUBMITTER: Futai E 

PROVIDER: S-EPMC2676034 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature