ZFIN ID: ZDB-PUB-121220-23
Amyloid Beta precursor protein and prion protein have a conserved interaction affecting cell adhesion and CNS development
Kaiser, D.M., Acharya, M., Leighton, P.L., Wang, H., Daude, N., Wohlgemuth, S., Shi, B., and Allison, W.T.
Date: 2012
Source: PLoS One   7(12): e51305 (Journal)
Registered Authors: Acharya, Moulinath, Allison, Ted, Kaiser, Darcy, Leighton, Patricia, Wang, Hao
Keywords: none
MeSH Terms:
  • Amyloid beta-Protein Precursor/genetics
  • Amyloid beta-Protein Precursor/metabolism*
  • Animals
  • Apoptosis/genetics
  • Apoptosis/physiology*
  • Cell Adhesion/physiology*
  • Central Nervous System/cytology
  • Central Nervous System/embryology*
  • Cloning, Molecular
  • DNA Primers/genetics
  • Gene Knockdown Techniques
  • Humans
  • Immunoprecipitation
  • Mice
  • Morpholinos/genetics
  • Mutagenesis, Site-Directed
  • Phenotype*
  • Prions/genetics
  • Prions/metabolism*
  • Zebrafish
PubMed: 23236467 Full text @ PLoS One
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ABSTRACT

Genetic and biochemical mechanisms linking onset or progression of Alzheimer Disease and prion diseases have been lacking and/or controversial, and their etiologies are often considered independent. Here we document a novel, conserved and specific genetic interaction between the proteins that underlie these diseases, amyloid-β precursor protein and prion protein, APP and PRP, respectively. Knockdown of APP and/or PRNP homologs in the zebrafish (appa, appb, prp1, and prp2) produces a dose-dependent phenotype characterized by systemic morphological defects, reduced cell adhesion and CNS cell death. This genetic interaction is surprisingly exclusive in that prp1 genetically interacts with zebrafish appa, but not with appb, and the zebrafish paralog prp2 fails to interact with appa. Intriguingly, appa & appb are largely redundant in early zebrafish development yet their abilities to rescue CNS cell death are differentially contingent on prp1 abundance. Delivery of human APP or mouse Prnp mRNAs rescue the phenotypes observed in app-prp-depleted zebrafish, highlighting the conserved nature of this interaction. Immunoprecipitation revealed that human APP and PrPC proteins can have a physical interaction. Our study reports a unique in vivo interdependence between APP and PRP loss-of-function, detailing a biochemical interaction that considerably expands the hypothesized roles of PRP in Alzheimer Disease.

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