Publication

Chaperone proteostasis in Parkinson's disease: stabilization of the Hsp70/alpha-synuclein complex by Hip

Roodveldt, C., Bertoncini, C. W., Andersson, A., van der Goot, A. T., Hsu, S-T., Fernandez-Montesinos, R., de Jong, J., van Ham, T. J., Nollen, E. A., Pozo, D., Christodoulou, J. & Dobson, C. M., 2-Dec-2009, In : EMBO Journal. 28, 23, p. 3758-3770 13 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Cintia Roodveldt
  • Carlos W. Bertoncini
  • August Andersson
  • Annemieke T. van der Goot
  • Shang-Te Hsu
  • Rafael Fernandez-Montesinos
  • Jannie de Jong
  • Tjakko J. van Ham
  • Ellen A. Nollen
  • David Pozo
  • John Christodoulou
  • Christopher M. Dobson

The ATP-dependent protein chaperone heat-shock protein 70 (Hsp70) displays broad anti-aggregation functions and has a critical function in preventing protein misfolding pathologies. According to in vitro and in vivo models of Parkinson's disease (PD), loss of Hsp70 activity is associated with neurodegeneration and the formation of amyloid deposits of alpha-synuclein (alpha Syn), which constitute the intraneuronal inclusions in PD patients known as Lewy bodies. Here, we show that Hsp70 depletion can be a direct result of the presence of aggregation-prone polypeptides. We show a nucleotide-dependent interaction between Hsp70 and alpha Syn, which leads to the aggregation of Hsp70, in the presence of ADP along with alpha Syn. Such a co-aggregation phenomenon can be prevented in vitro by the co-chaperone Hip (ST13), and the hypothesis that it might do so also in vivo is supported by studies of a Caenorhabditis elegans model of alpha Syn aggregation. Our findings indicate that a decreased expression of Hip could facilitate depletion of Hsp70 by amyloidogenic polypeptides, impairing chaperone proteostasis and stimulating neurodegeneration. The EMBO Journal (2009) 28, 3758-3770. doi: 10.1038/emboj.2009.298; Published online 29 October 2009

Original languageEnglish
Pages (from-to)3758-3770
Number of pages13
JournalEMBO Journal
Volume28
Issue number23
Publication statusPublished - 2-Dec-2009

    Keywords

  • amyloid, Hip, Hsp70, Parkinson's disease, alpha-synuclein, SYNUCLEIN FIBRIL FORMATION, HEAT-SHOCK-PROTEIN, ALPHA-SYNUCLEIN, MOLECULAR CHAPERONES, HSP70 CHAPERONES, ESCHERICHIA-COLI, PEPTIDE-BINDING, GENE-EXPRESSION, REACTION CYCLE, AGGREGATION

ID: 4991776