Functional screening in Drosophila reveals the conserved role of REEP1 in promoting stress resistance and preventing the formation of Tau aggregates

Chiara Appocher; Raffaella Klima; Fabian Feiguin

doi:10.1093/hmg/ddu393

Functional screening in Drosophila reveals the conserved role of REEP1 in promoting stress resistance and preventing the formation of Tau aggregates

Hum Mol Genet. 2014 Dec 20;23(25):6762-72. doi: 10.1093/hmg/ddu393. Epub 2014 Aug 5.

Authors

Chiara Appocher¹, Raffaella Klima¹, Fabian Feiguin²

Affiliations

¹ International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste 34149, Italy.
² International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste 34149, Italy [email protected] [email protected].

PMID: 25096240
DOI: 10.1093/hmg/ddu393

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Conserved Sequence
Drosophila Proteins / chemistry
Drosophila Proteins / genetics*
Drosophila Proteins / metabolism
Drosophila melanogaster / genetics*
Drosophila melanogaster / metabolism
Endoplasmic Reticulum Stress / genetics*
Eye / cytology
Eye / metabolism
Eye Proteins / genetics
Eye Proteins / metabolism
Gene Expression Regulation
Genotype
High-Throughput Screening Assays
Membrane Transport Proteins / chemistry
Membrane Transport Proteins / genetics*
Membrane Transport Proteins / metabolism
Microtubules / chemistry
Microtubules / metabolism
Molecular Sequence Data
Neurons / cytology
Neurons / metabolism*
Phenotype
Protein Aggregates
RNA Interference
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Signal Transduction
tau Proteins / chemistry
tau Proteins / genetics*
tau Proteins / metabolism

Substances

Drosophila Proteins
Eye Proteins
Membrane Transport Proteins
Protein Aggregates
REEP1 protein, human
RNA, Small Interfering
ReepA protein, Drosophila
tau Proteins