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

61 Citations (Scopus)

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 - 2011
Externally publishedYes

Fingerprint

Endoplasmic Reticulum-Associated Degradation
endoplasmic reticulum
Endoplasmic Reticulum Stress
degradation
Degradation
Down-Regulation
Cystic Fibrosis Transmembrane Conductance Regulator
Dystonia
Cholera Toxin
Nuclear Envelope
Endoplasmic Reticulum
Adenosine Triphosphatases
Fibroblasts
Torsional stress
cystic fibrosis
cholera
lumens
regulators
fibroblasts
Proteins

ASJC Scopus subject areas

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

Cite this

Nery, F. C., Armata, I. A., Farley, J. E., Cho, J. A., Yaqub, U., Chen, P., ... Breakefield, X. O. (2011). TorsinA participates in endoplasmic reticulum-associated degradation. Nature Communications, 2(1), [393]. https://doi.org/10.1038/ncomms1383

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

In: Nature Communications, Vol. 2, No. 1, 393, 2011.

Research output: Contribution to journalArticle

Nery, FC, Armata, IA, Farley, JE, Cho, JA, Yaqub, U, Chen, P, Da Hora, CC, Wang, Q, Tagaya, M, Klein, C, Tannous, B, Caldwell, KA, Caldwell, GA, Lencer, WI, Ye, Y & Breakefield, XO 2011, 'TorsinA participates in endoplasmic reticulum-associated degradation', Nature Communications, vol. 2, no. 1, 393. https://doi.org/10.1038/ncomms1383
Nery, Flávia C. ; Armata, Ioanna A. ; Farley, Jonathan E. ; Cho, Jin A. ; Yaqub, Uzma ; Chen, Pan ; Da Hora, Cintia Carla ; Wang, Qiuyan ; Tagaya, Mitsuo ; Klein, Christine ; Tannous, Bakhos ; Caldwell, Kim A. ; Caldwell, Guy A. ; Lencer, Wayne I. ; Ye, Yihong ; Breakefield, Xandra O. / TorsinA participates in endoplasmic reticulum-associated degradation. In: Nature Communications. 2011 ; Vol. 2, No. 1.
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