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.


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


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