Neuron-to-Neuron Transfer of FUS in Drosophila Primary Neuronal Culture Is Enhanced by ALS-Associated Mutations

Sébastien Feuillette, Morgane Delarue, Gaëtan Riou, Anne Lise Gaffuri, Jane Wu, Zsolt Lenkei, Olivier Boyer, Thierry Frébourg, Dominique Campion, Magalie Lecourtois*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The DNA- and RNA-binding protein fused in sarcoma (FUS) has been pathologically and genetically linked to amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration (FTLD). Cytoplasmic FUS-positive inclusions were identified in the brain and spinal cord of a subset of patients suffering with ALS/FTLD. An increasing number of reports suggest that FUS protein can behave in a prion-like manner. However, no neuropathological studies or experimental data were available regarding cell-to-cell spread of these pathological protein assemblies. In the present report, we investigated the ability of wild-type and mutant forms of FUS to transfer between neuronal cells. We combined the use of Drosophila models for FUS proteinopathies with that of the primary neuronal cultures to address neuron-to-neuron transfer of FUS proteins. Using conditional co-culture models and an optimized flow cytometry-based methodology, we demonstrated that ALS-mutant forms of FUS proteins can transfer between well-differentiated mature Drosophila neurons. These new observations support that a propagating mechanism could be applicable to FUS, leading to the sequential dissemination of pathological proteins over years.

Original languageEnglish (US)
Pages (from-to)114-122
Number of pages9
JournalJournal of Molecular Neuroscience
Volume62
Issue number1
DOIs
StatePublished - May 1 2017

Keywords

  • Drosophila primary neuronal culture
  • FACS
  • FUS
  • Mutations
  • Spreading

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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