title: Identifying genes that interact with Drosophila presenilin and amyloid precursor protein.
abstract: The gamma-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 gamma-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.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Diana L
authors.initials: DL
authors.lastname: van de Hoef
authors.forename: James
authors.initials: J
authors.lastname: Hughes
authors.forename: Izhar
authors.initials: I
authors.lastname: Livne-Bar
authors.forename: Dan
authors.initials: D
authors.lastname: Garza
authors.forename: Mary
authors.initials: M
authors.lastname: Konsolaki
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Boulianne
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005260:Female; D008297:Male; D008565:Membrane Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins; D010641:Phenotype; D053763:Presenilins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; C066839:Appl protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D009419:Nerve Tissue Proteins; D053763:Presenilins; D051880:Receptors, Notch