A single tyrosine residue in the amyloid precursor protein intracellular domain is essential for developmental function

Abstract

The Aβ-precursor protein (APP) intracellular domain is highly conserved and contains many potentially important residues, in particular the 682YENPTY687 motif. To dissect the functions of this sequence in vivo, we created an APP knock-in allele mutating Tyr682 to Gly (Y682G). Crossing this allele to APP-like protein 2 (APLP2) knock-out background showed that mutation of Tyr682 results in postnatal lethality and neuromuscular synapse defects similar to doubly deficient APP/APLP2 mice. Our results demonstrate that a single residue in the APP intracellular region, Tyr682, is indispensable for the essential function of APP in developmental regulation. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.