title: Intracellular calcium deficits in Drosophila cholinergic neurons expressing wild type or FAD-mutant presenilin.
abstract: Much of our current understanding about neurodegenerative diseases can be attributed to the study of inherited forms of these disorders. For example, mutations in the presenilin 1 and 2 genes have been linked to early onset familial forms of Alzheimer's disease (FAD). Using the Drosophila central nervous system as a model we have investigated the role of presenilin in one of the earliest cellular defects associated with Alzheimer's disease, intracellular calcium deregulation. We show that expression of either wild type or FAD-mutant presenilin in Drosophila CNS neurons has no impact on resting calcium levels but does give rise to deficits in intracellular calcium stores. Furthermore, we show that a loss-of-function mutation in calmodulin, a key regulator of intracellular calcium, can suppress presenilin-induced deficits in calcium stores. Our data support a model whereby presenilin plays a role in regulating intracellular calcium stores and demonstrate that Drosophila can be used to study the link between presenilin and calcium deregulation.
authors.affiliation: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Kinga
authors.initials: K
authors.lastname: Michno
authors.forename: David
authors.initials: D
authors.lastname: Knight
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Campusano
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Campussano
authors.forename: Diana
authors.initials: D
authors.lastname: van de Hoef
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Boulianne
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003433:Crosses, Genetic; D004331:Drosophila melanogaster / Q000378:metabolism*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005786:Gene Expression Regulation; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D053763:Presenilins / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D019076:Transgenes
chemical_list: D000596:Amino Acids; D053763:Presenilins; D005182:Flavin-Adenine Dinucleotide; D002118:Calcium