Biosynthesis of the dystonia-associated AAA+ ATPase torsinA at the endoplasmic reticulum

• Published in: Biochemical journal Vol. 401; no. 2; pp. 607 - 612
• Main Authors: Callan, Anna C, Bunning, Sandra, Jones, Owen T, High, Stephen, Swanton, Eileithyia
• Format: Journal Article
• Language: English
• Published: England Portland Press 15.01.2007; Portland Press Ltd
• Subjects: Adenosine Triphosphatases - biosynthesis; Amino Acid Sequence; Cell-Free System; Endoplasmic Reticulum - metabolism; HeLa Cells; Humans; Membrane Proteins - metabolism; Molecular Chaperones - biosynthesis; Protein Transport; Serine Endopeptidases - metabolism; Life Sciences
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj20061313

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.