Journal
JOURNAL OF CELL SCIENCE
Volume 121, Issue 11, Pages 1832-1840Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.020321
Keywords
tail-anchored protein; RAMP4; Sec61 beta; cytochrome b5; endoplasmic reticulum; Asna-1/TRC40
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Funding
- Wellcome Trust [081671] Funding Source: Medline
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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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