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

Anna C Callan , Sandra Bunning , Owen T Jones , Stephen High , Eileithyia Swanton (1)

1 Faculty of Life Sciences [Manchester]

TorsinA is a widely expressed AAA +} 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 endoplasmic reticulum (ER) lumen. However, we now 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 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.

Mots clés: Life Sciences

Anna C Callan, Sandra Bunning, Owen T Jones, Stephen High, Eileithyia Swanton. Biosynthesis of the dystonia-associated AAA +} ATPase torsinA at the endoplasmic reticulum. Biochemical Journal, 2006, 401 (2), pp.607-612. ⟨10.1042/BJ20061313⟩. ⟨hal-00478653⟩