C9orf72-generated poly-GR and poly-PR do not directly interfere with nucleocytoplasmic transport

Sci Rep. 2019 Oct 31;9(1):15728. doi: 10.1038/s41598-019-52035-6.

Abstract

Repeat expansions in the C9orf72 gene cause amyotrophic lateral sclerosis and frontotemporal dementia characterized by dipeptide-repeat protein (DPR) inclusions. The toxicity associated with two of these DPRs, poly-GR and poly-PR, has been associated with nucleocytoplasmic transport. To investigate the causal role of poly-GR or poly-PR on active nucleocytoplasmic transport, we measured nuclear import and export in poly-GR or poly-PR expressing Hela cells, neuronal-like SH-SY5Y cells and iPSC-derived motor neurons. Our data strongly indicate that poly-GR and poly-PR do not directly impede active nucleocytoplasmic transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus* / drug effects
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology
  • C9orf72 Protein / genetics
  • C9orf72 Protein / metabolism*
  • Cell Line, Tumor
  • DNA Repeat Expansion
  • Dipeptides / genetics
  • Dipeptides / metabolism
  • Exportin 1 Protein
  • Fatty Acids, Unsaturated / pharmacology
  • Frontotemporal Dementia / metabolism
  • Frontotemporal Dementia / pathology
  • Genes, Regulator
  • HeLa Cells
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Karyopherins / antagonists & inhibitors
  • Karyopherins / genetics
  • Microscopy, Fluorescence
  • Motor Neurons / cytology
  • Motor Neurons / metabolism
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / genetics

Substances

  • C9orf72 Protein
  • Dipeptides
  • Fatty Acids, Unsaturated
  • Karyopherins
  • Receptors, Cytoplasmic and Nuclear
  • leptomycin B