TorsinA is a widely expressed AAA+ (ATPases associated with various cellular activities) ATPase of unknown function. Previous studies have described torsinA as a type II protein with a cleavable signal sequence, a single membrane spanning domain, and its C-terminus located in the ER (endoplasmic reticulum) lumen. However, in the present study we show that torsinA is not in fact an integral membrane protein. Instead we find that the mature protein associates peripherally with the ER membrane, most likely through an interaction with an integral membrane protein. Consistent with this model, we provide evidence that the signal peptidase complex cleaves the signal sequence of torsinA, and we show that the region previously suggested to form a transmembrane domain is translocated into the lumen of the ER. The finding that torsinA is a peripheral, and not an integral membrane protein as previously thought, has important implications for understanding the function of this novel ATPase.
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Research Article|
December 21 2006
Biosynthesis of the dystonia-associated AAA+ ATPase torsinA at the endoplasmic reticulum
Anna C. Callan;
Anna C. Callan
1Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
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Sandra Bunning;
Sandra Bunning
1Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
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Owen T. Jones;
Owen T. Jones
1Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
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Stephen High;
Stephen High
1Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
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Eileithyia Swanton
Eileithyia Swanton
1
1Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
1To whom correspondence should be addressed (email lisa.swanton@manchester.ac.uk).
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Publisher: Portland Press Ltd
Received:
August 30 2006
Revision Received:
October 12 2006
Accepted:
October 12 2006
Accepted Manuscript online:
October 12 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2007
Biochem J (2007) 401 (2): 607–612.
Article history
Received:
August 30 2006
Revision Received:
October 12 2006
Accepted:
October 12 2006
Accepted Manuscript online:
October 12 2006
Citation
Anna C. Callan, Sandra Bunning, Owen T. Jones, Stephen High, Eileithyia Swanton; Biosynthesis of the dystonia-associated AAA+ ATPase torsinA at the endoplasmic reticulum. Biochem J 15 January 2007; 401 (2): 607–612. doi: https://doi.org/10.1042/BJ20061313
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