The Role of Post-Translational Modifications on Prion-Like Aggregation and Liquid-Phase Separation of FUS

Int J Mol Sci. 2018 Mar 16;19(3):886. doi: 10.3390/ijms19030886.

Abstract

Subcellular mislocalization and aggregation of the human FUS protein occurs in neurons of patients with subtypes of amyotrophic lateral sclerosis and frontotemporal dementia. FUS is one of several RNA-binding proteins that can functionally self-associate into distinct liquid-phase droplet structures. It is postulated that aberrant interactions within the dense phase-separated state can potentiate FUS's transition into solid prion-like aggregates that cause disease. FUS is post-translationally modified at numerous positions, which affect both its localization and aggregation propensity. These modifications may influence FUS-linked pathology and serve as therapeutic targets.

Keywords: ALS; FTLD; FUS; LLPS; amyloid; prion.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / metabolism
  • Animals
  • Frontotemporal Dementia / metabolism
  • Humans
  • Inclusion Bodies / chemistry
  • Inclusion Bodies / metabolism
  • Mutation
  • Neurons / metabolism
  • Prion Proteins / chemistry
  • Prion Proteins / metabolism*
  • Protein Aggregates*
  • Protein Aggregation, Pathological / metabolism*
  • Protein Processing, Post-Translational*
  • RNA-Binding Protein FUS / chemistry
  • RNA-Binding Protein FUS / metabolism*

Substances

  • FUS protein, human
  • Prion Proteins
  • Protein Aggregates
  • RNA-Binding Protein FUS