Interaction of ataxin-3 with huntingtin-associated protein 1 through Josephin domain

Neuroreport. 2011 Mar 30;22(5):232-8. doi: 10.1097/WNR.0b013e32834505f4.


Huntingtin-associated protein 1 (HAP1) is an essential component of the stigmoid body (STB) and known as a possible neuroprotective interactor with causative proteins for Huntington's disease, spinal and bulbar muscular atrophy, spinocerebellar ataxia type 17 (SCA17), and Joubert syndrome. To clarify what other causative molecules HAP1/STB could interact with, we cloned normal causative genes for several neural disorders from human brain RNA library and evaluated their subcellular interaction with HAP1/STB by immunocytochemistry and immunoprecipitation after cotransfection into Neuro2a cells. The results clearly showed that HAP1/STB interacts with the normal ataxin-3 through Josephin domain and polyglutamine-expanded mutants derived from SCA3 as well. The findings suggest that HAP1/STB could modify the physiological function of normal ataxin-3 and pathogenesis of SCA3 attributable to the mutant ataxin-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxin-3
  • Blotting, Western
  • Humans
  • Immunoprecipitation
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinocerebellar Ataxias / metabolism
  • Transfection


  • HAP1 protein, human
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • ATXN3 protein, human
  • Ataxin-3