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Exploring the Influence of TorsinA Expression on Protein Quality Control

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Abstract

DYT1 dystonia is caused by a glutamic acid deletion (ΔE) in the endoplasmic reticulum (ER) protein torsinA. Previous studies suggest that torsinA modulates the aggregation of cytosolic misfolded proteins and ER stress responses, although the mechanisms underlying those effects remain unclear. In order to investigate the bases of these observations, we analyzed the interaction between torsinA expression, protein aggregation and ER stress in PC6.3 cells. Unexpectedly, we found that expression of torsinA(wt) or (ΔE) does not influence the inclusion formation by an expanded polyglutamine reporter protein in this cellular model. Furthermore, torsinA does not prevent the activation of ER stress induced by thapsigargin or the reducing agent DTT. Interestingly, DTT induces post-translational changes in torsinA, more prominently for torsinA(wt) than (ΔE). This work highlights the importance of model system selection for the study of torsinA function. Furthermore, it provides additional evidence suggesting that torsinA is sensitive to changes in the cellular redox potential.

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Acknowledgments

This work was supported by NIH/NINDS (K02NS058450) (PGA) and VA Research Career Development Award 2006-12 (KAG).We would like to thank all the members of the Gonzalez-Alegre and Glenn labs for helpful comments and Drs. H. Paulson and D.T. Rutkowski for helpful comments and reagents.

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Authors and Affiliations

  1. Graduate Program in Neuroscience, The University of Iowa, Iowa City, IA, USA

    Kara L. Gordon & Pedro Gonzalez-Alegre

  2. Veterans Administration Hospital, Iowa City, IA, USA

    Kevin A. Glenn

  3. Department of Internal Medicine, The University of Iowa, Iowa City, IA, 52242, USA

    Kevin A. Glenn

  4. Department of Neurology, Carver College of Medicine, The University of Iowa, 3111A MERF, 375 Newton Road, Iowa City, IA, 52242, USA

    Pedro Gonzalez-Alegre

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  1. Kara L. Gordon
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Correspondence to Pedro Gonzalez-Alegre.

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Gordon, K.L., Glenn, K.A. & Gonzalez-Alegre, P. Exploring the Influence of TorsinA Expression on Protein Quality Control. Neurochem Res 36, 452–459 (2011). https://doi.org/10.1007/s11064-010-0363-4

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