Phosphorylation of α-synuclein is crucial in compensating for proteasomal dysfunction

Hee soon Choi, Hyunjeong Liew, Ahram Jang, Yun Mi Kim, Hilal Lashuel, Yoo Hun Suh

Research output: Contribution to journalArticle

7 Citations (Scopus)


α-Synuclein can be degraded by both the ubiquitin-proteasomal system and the chaperone-lysosomal system. However, the switching mechanism between the two pathways is not clearly understood. In our study, we investigated the mutual association between the binding of α-synuclein to heat shock cognate 70 and the lysosomal translocation of α-synuclein. Tyrosine phosphorylation of Y136 on α-synuclein increased when it bound to heat shock protein 70. We also found that tyrosine phosphorylation of α-synuclein can be regulated by focal adhesion kinase pp125 and protein tyrosine phosphatase 1B. Furthermore, protein tyrosine phosphatase 1B inhibitor protected dopaminergic neurons against cell death and rescued rotarod performance in a Parkinson's disease animal model. This study provides evidence that the regulation of Y136 phosphorylation of α-synuclein can improve behavioral performance and protect against neuronal death by promoting the turnover of lysosomal degradation of α-synuclein. As a result, protein tyrosine phosphatase 1B inhibitor may be used as a potential therapeutic agent against Parkinson's disease.

Original languageEnglish
Pages (from-to)597-603
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 3 Aug 2012



  • HSC70
  • Lysosome
  • Phosphorylation
  • Proteasome
  • α-Synuclein

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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