title: Functional screening in Drosophila reveals the conserved role of REEP1 in promoting stress resistance and preventing the formation of Tau aggregates.
abstract: Pathological modifications in the microtubule-associated protein Tau is a common characteristic observed in different neurological diseases, suggesting that analogous metabolic pathways might be similarly affected during neurodegeneration. To identify these molecules and mechanisms, we utilized Drosophila models of human Tau-mediated neurodegeneration to perform an RNA interference functional screening against genes considered to be implicated in the pathogenesis of different neurodegenerative disorders. We found that the downregulation of the Drosophila REEP1 homolog protein enhanced Tau toxicity with increased formation of insoluble aggregates. On the contrary, the overexpression of either the Drosophila or the human REEP1 protein was able to revert these phenotypes and promote neuronal resistance to ER stress. These studies identify a new function for the REEP1 protein in vivo and a novel cellular mechanism to prevent Tau toxicity.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste 34149, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Appocher
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste 34149, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Klima
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste 34149, Italy fabian.feiguin@icgeb.org feiguin@icgeb.org.
authors.forename: Fabian
authors.initials: F
authors.lastname: Feiguin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D005123:Eye / Q000166:cytology / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005838:Genotype; D057166:High-Throughput Screening Assays; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D066329:Protein Aggregates; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D005136:Eye Proteins; D026901:Membrane Transport Proteins; D066329:Protein Aggregates; C495318:REEP1 protein, human; D034741:RNA, Small Interfering; C000599331:ReepA protein, Drosophila; D016875:tau Proteins