X11 alpha and x11 beta interact with presenilin-1 via their PDZ domains

X11 alpha and X11 beta are two neuronal adaptor proteins that interact with the Alzheimer's disease amyloid precursor protein (APP). X11 alpha and X11 beta stabilise APP and inhibit production of proteolytic APP fragments inc luding the AP peptide that is deposited in the brains of Alzheimer's diseas e patients. The mechanisms by which X11 alpha and X11 beta modulate APP pro cessing are not clear but one possibility is that they influence the activi ty of the secretases that cleave APP to give rise to A beta. Presenilin-1 i s required for gamma -secretase activity and here we demonstrate that both X11 alpha and X11 beta interact with presenilin-1. X11/presenilin-1 binding is via two X11 PDZ domains and sequences within the carboxy-terminus of pr esenilin-1. We also demonstrate that both X11 alpha and X11 beta mediate th e formation of complexes between APP and presenilin-1. These results sugges t that the X11 regulation of APP processing is controlled, at least in part , via their interactions with APP and presenilin-1.