A Single Tyrosine Residue in the Amyloid Precursor Protein Intracellular Domain Is Essential for Developmental Function

The A beta-precursor protein (APP) intracellular domain is highly conserved and contains many potentially important residues, in particular the (YENPTY687)-Y-682 motif. To dissect the functions of this sequence in vivo, we created an APP knock-in allele mutating Tyr(682) to Gly (Y682G). Crossing this allele to APP-like protein 2 (APLP2) knock-out background showed that mutation of Tyr(682) 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, Tyr(682), is indispensable for the essential function of APP in developmental regulation.