Identification of syntaxin 1A as a novel binding protein for presenilin-1

Mutations in the presenilin 1 gene have been shown to result in Alzheimer's disease. Presenilin 1 is a multi-transmembrane protein with a large hydrop hilic loop near the C-terminus. This region is required for known functions of presenilin 1. We have constrained this loop within the active site of t he bacterial protein, thioredoxin, to mimic its native conformational state . This hybrid protein was used as bait in a yeast two hybrid screen in an a ttempt to identify presenilin binding proteins. By this method syntaxin 1A, a synaptic plasma membrane protein, was identified as a novel binding prot ein for presenilin 1. In vitro experiments confirm the two-hybrid results s uggesting that PSI binds syntaxin under physiological conditions. (C) 2000 Elsevier Science B.V. All rights reserved.