Nuclear localization of alpha-synuclein and its interaction with histones

Biochemistry. 2003 Jul 22;42(28):8465-71. doi: 10.1021/bi0341152.

Abstract

The aggregation of alpha-synuclein is believed to play an important role in the pathogenesis of Parkinson's disease as well as other neurodegenerative disorders ("synucleinopathies"). However, the function of alpha-synuclein under physiologic and pathological conditions is unknown, and the mechanism of alpha-synuclein aggregation is not well understood. Here we show that alpha-synuclein forms a tight 2:1 complex with histones and that the fibrillation rate of alpha-synuclein is dramatically accelerated in the presence of histones in vitro. We also describe the presence of alpha-synuclein and its co-localization with histones in the nuclei of nigral neurons from mice exposed to a toxic insult (i.e., injections of the herbicide paraquat). These observations indicate that translocation into the nucleus and binding with histones represent potential mechanisms underlying alpha-synuclein pathophysiology.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Nucleus / metabolism*
  • Cloning, Molecular
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression Regulation / drug effects
  • Histones / metabolism*
  • Humans
  • Kinetics
  • Microscopy, Electron
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / ultrastructure
  • Paraquat / pharmacology
  • Protein Binding
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / ultrastructure
  • Synucleins
  • alpha-Synuclein

Substances

  • Histones
  • Nerve Tissue Proteins
  • Recombinant Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein
  • Paraquat