title: The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for developmental function.
abstract: BACKGROUND
  Processing of Aβ-precursor protein (APP) plays an important role in Alzheimer's Disease (AD) pathogenesis. Thr residue at amino acid 668 of the APP intracellular domain (AID) is highly conserved. When phosphorylated, this residue generates a binding site for Pin1. The interaction of APP with Pin1 has been involved in AD pathogenesis.
  
  
  RESULTS
  To dissect the functions of this sequence in vivo, we created an APP knock-in allele, in which Thr(668) is replaced by an Ala (T(668)A). Doubly deficient APP/APP-like protein 2 (APLP2) mice present postnatal lethality and neuromuscular synapse defects. Previous work has shown that the APP intracellular domain is necessary for preventing early lethality and neuromuscular junctions (NMJ) defects. Crossing the T(668)A allele into the APLP2 knockout background showed that mutation of Thr(668) does not cause a defective phenotype. Notably, the T(668)A mutant APP is able to bind Mint1.
  
  
  CONCLUSIONS
  Our results argue against an important role of the Thr(668) residue in the essential function of APP in developmental regulation. Furthermore, they indicate that phosphorylation at this residue is not functionally involved in those APP-mediated functions that prevent (NMJ) defects and early lethality in APLP2 null mice.
authors: Department of Microbiology and Immunology, Einstein College of Medicine, Bronx, New York, United States of America.
authors: Alessia P M
authors: AP
authors: Barbagallo
authors: Zilai
authors: Z
authors: Wang
authors: Hui
authors: H
authors: Zheng
authors: Luciano
authors: L
authors: D'Adamio
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D005455:Fluorescent Antibody Technique; D051379:Mice; D008810:Mice, Inbred C57BL; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D013912:Threonine; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse