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

The APP intracellular domain (AID) is highly conserved and contains many potentially important residues, in particular the 682YENPTY687 motif. To dissect the function of this sequence in vivo, we created an APP knock-in allele mutating Y682 to Gly (Y682G). Crossing this allele to APP-like protein 2 (APLP2) knockout background showed that, mutation of Y682 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, Y682, is indispensible for the essential function of APP in developmental regulation.