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JCS ePress online publication date 13 May 2008
doi: 10.1242/jcs.020321

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Research Article

Distinct targeting pathways for the membrane insertion of tail-anchored (TA) proteins


Vincenzo Favaloro, Milan Spasic, Blanche Schwappach, and Bernhard Dobberstein*
* Author for correspondence (e-mail: b.dobberstein{at}zmbh.uni-heidelberg.de)

Tail-anchored (TA) proteins are characterised by a C-terminal transmembrane region that mediates post-translational insertion into the membrane of the endoplasmic reticulum (ER). We have investigated the requirements for membrane insertion of three TA proteins, RAMP4, Sec61{beta} and cytochrome b5. We show here that newly synthesised RAMP4 and Sec61{beta} can accumulate in a cytosolic, soluble complex with the ATPase Asna1 before insertion into ER-derived membranes. Membrane insertion of these TA proteins is stimulated by ATP, sensitive to redox conditions and blocked by alkylation of SH groups by N-ethylmaleimide (NEM). By contrast, membrane insertion of cytochrome b5 is not found to be mediated by Asna1, not stimulated by ATP and not affected by NEM or an oxidative environment. The Asna1-mediated pathway of membrane insertion of RAMP4 and Sec61{beta} may relate to functions of these proteins in the ER stress response.


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