A single tyrosine residue in the amyloid precursor protein intracellular domain is essential for developmental function.
The Aβ-precursor protein (APP) intracellular domain is highly conserved and contains many potentially important residues, in particular the (682)YENPTY(687) 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.
Department of Microbiology and Immunology, Einstein College of Medicine, Bronx, New York 10461, USA.
Alessia P M
AP
Barbagallo
Zilai
Z
Wang
Hui
H
Zheng
Luciano
L
D'Adamio
D000483:Alleles; D020816:Amino Acid Motifs; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D055879:Gene Knock-In Techniques; D051379:Mice; D018345:Mice, Knockout; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; C492952:Aplp2 protein, mouse; D014443:Tyrosine
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