Metabolism of amyloid precursor protein in COS cells transfected with a beta-secretase candidate

Thimet oligopeptidase (TOP) is a thiol- and metallo-dependent peptidase and has been shown to be one of the beta-secretase candidates. TOP expressed i n COS cells cleaved amyloid precursor protein (APP) at the beta-secretase s ite, and we found a proteolytic product of APP called secreted form of APP by beta-secretase (sAPP beta) in the conditioned media. Here we demonstrate that sAPP beta was increased in conditioned media when TOP was coexpressed in COS cells with APP and treated with an ADAM inhibitor SI-27. In additio n, although TOP expressed in COS cell was localized at nuclei or Golgi appa ratus, it exclusively colocalized at Golgi apparatus when APP was coexpress ed with TOP.