Open Access Research article

ERAD and protein import defects in a sec61 mutant lacking ER-lumenal loop 7

Thomas Tretter1, Fábio P Pereira1, Ozlem Ulucan2, Volkhard Helms2, Susanne Allan3, Kai-Uwe Kalies3 and Karin Römisch1*

Author Affiliations

1 Department of Microbiology, Faculty of Natural Sciences and Technology VIII, Saarland University, Campus A1.5, 66123 Saarbrücken, Germany

2 Center for Bioinformatics, Faculty of Natural Sciences and Technology VIII, Saarland University, 66123 Saarbrücken, Germany

3 Faculty of Biology, University of Lübeck, Lübeck, Germany

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BMC Cell Biology 2013, 14:56  doi:10.1186/1471-2121-14-56

Published: 6 December 2013



The Sec61 channel mediates protein translocation across the endoplasmic reticulum (ER) membrane during secretory protein biogenesis, and likely also during export of misfolded proteins for ER-associated degradation (ERAD). The mechanisms of channel opening for the different modes of translocation are not understood so far, but the position of the large ER-lumenal loop 7 of Sec61p suggests a decisive role.


We show here that the Y345H mutation in L7 which causes diabetes in the mouse displays no ER import defects in yeast, but a delay in misfolded protein export. A complete deletion of L7 in Sec61p resulted in viable, cold- and tunicamycin-hypersensitive yeast cells with strong defects in posttranslational protein import of soluble proteins into the ER, and in ERAD of soluble substrates. Membrane protein ERAD was only moderately slower in sec61∆L7 than in wildtype cells. Although Sec61∆L7 channels were unstable in detergent, co-translational protein integration into the ER membrane, proteasome binding to Sec61∆L7 channels, and formation of hetero-heptameric Sec complexes were not affected.


We conclude that L7 of Sec61p is required for initiation of posttranslational soluble protein import into and misfolded soluble protein export from the ER, suggesting a key role for L7 in transverse gating of the Sec61 channel.

Protein translocation; Endoplasmic Reticulum; Sec61 channel; ERAD