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

doi:10.1038/ncomms1383

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 journal › Article › peer-review

88 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 language	English (US)
Article number	393
Journal	Nature communications
Volume	2
Issue number	1
DOIs	https://doi.org/10.1038/ncomms1383
State	Published - 2011
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms1383

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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), Article 393. https://doi.org/10.1038/ncomms1383

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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 (CFTR{\^I} {"}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 CFTR{\^I} {"}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.",

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AU - Nery, Flávia C.

AU - Armata, Ioanna A.

AU - Farley, Jonathan E.

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AU - Yaqub, Uzma

AU - Chen, Pan

AU - Da Hora, Cintia Carla

AU - Wang, Qiuyan

AU - Tagaya, Mitsuo

AU - Klein, Christine

AU - Tannous, Bakhos

AU - Caldwell, Kim A.

AU - Caldwell, Guy A.

AU - Lencer, Wayne I.

AU - Ye, Yihong

AU - Breakefield, Xandra O.

PY - 2011

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TorsinA participates in endoplasmic reticulum-associated degradation

Abstract

ASJC Scopus subject areas

UN SDGs

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