Identifying genes that interact with Drosophila presenilin and amyloid precursor protein

Diana L. van de Hoef, James Hughes, Izhar Livne-Bar, Dan Garza, Mary Konsolaki, Gabrielle L. Boulianne

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The γ-secretase complex is involved in cleaving transmembrane proteins such as Notch and one of the genes targeted in Alzheimer's disease known as amyloid precursor protein (APP). Presenilins function within the catalytic core of γ-secretase, and mutated forms of presenilins were identified as causative factors in familial Alzheimer's disease. Recent studies show that in addition to Notch and APP, numerous signal transduction pathways are modulated by presenilins, including intracellular calcium signaling. Thus, presenilins appear to have diverse roles. To further understand presenilin function, we searched for Presenilin-interacting genes in Drosophila by performing a genetic modifier screen for enhancers and suppressors of Presenilin-dependent Notch-related phenotypes. We identified 177 modifiers, including known members of the Notch pathway and genes involved in intracellular calcium homeostasis. We further demonstrate that 53 of these modifiers genetically interacted with APP. Characterization of these genes may provide valuable insights into Presenilin function in development and disease.

Original languageEnglish (US)
Pages (from-to)246-260
Number of pages15
JournalGenesis
Volume47
Issue number4
DOIs
StatePublished - Jun 3 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Endocrinology
  • Cell Biology

Keywords

  • APP Drosophila
  • Alzheimer's disease
  • Genetic modifier
  • Presenilin

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