TorsinA participates in endoplasmic reticulum-associated degradation

Flávia C. Nery, Ioanna A. Armata, Jonathan E. Farley, Jin A. Cho, Uzma Yaqub, Pan Chen, Cintia Carla Da Hora, Qiuyan Wang, Mitsuo Tagaya, Christine Klein, Bakhos Tannous, Kim A. Caldwell, Guy A. Caldwell, Wayne I. Lencer, Yihong Ye, Xandra O. Breakefield

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

TorsinA is an AAA+ ATPase located within the lumen of the endoplasmic reticulum and nuclear envelope, with a mutant form causing early onset torsion dystonia (DYT1). Here we report a new function for torsinA in endoplasmic reticulum-associated degradation (ERAD). Retro-translocation and proteosomal degradation of a mutant cystic fibrosis transmembrane conductance regulator (CFTRÎ "F508) was inhibited by downregulation of torsinA or overexpression of mutant torsinA, and facilitated by increased torsinA. Retro-translocation of cholera toxin was also decreased by downregulation of torsinA. TorsinA associates with proteins implicated in ERAD, including Derlin-1, VIMP and p97. Further, torsinA reduces endoplasmic reticulum stress in nematodes overexpressing CFTRÎ "F508, and fibroblasts from DYT1 dystonia patients are more sensitive than controls to endoplasmic reticulum stress and less able to degrade mutant CFTR. Therefore, compromised ERAD function in the cells of DYT1 patients may increase sensitivity to endoplasmic reticulum stress with consequent alterations in neuronal function contributing to the disease state.

Original languageEnglish (US)
Article number393
JournalNature communications
Volume2
Issue number1
DOIs
StatePublished - Jul 19 2011
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'TorsinA participates in endoplasmic reticulum-associated degradation'. Together they form a unique fingerprint.

  • Cite this

    Nery, F. C., Armata, I. A., Farley, J. E., Cho, J. A., Yaqub, U., Chen, P., Da Hora, C. C., Wang, Q., Tagaya, M., Klein, C., Tannous, B., Caldwell, K. A., Caldwell, G. A., Lencer, W. I., Ye, Y., & Breakefield, X. O. (2011). TorsinA participates in endoplasmic reticulum-associated degradation. Nature communications, 2(1), [393]. https://doi.org/10.1038/ncomms1383