| First Author | Schäuble N | Year | 2012 |
| Journal | EMBO J | Volume | 31 |
| Issue | 15 | Pages | 3282-96 |
| PubMed ID | 22796945 | Mgi Jnum | J:188521 |
| Mgi Id | MGI:5440804 | Doi | 10.1038/emboj.2012.189 |
| Citation | Schauble N, et al. (2012) BiP-mediated closing of the Sec61 channel limits Ca2+ leakage from the ER. EMBO J 31(15):3282-96 |
| abstractText | In mammalian cells, signal peptide-dependent protein transport into the endoplasmic reticulum (ER) is mediated by a dynamic protein-conducting channel, the Sec61 complex. Previous work has characterized the Sec61 channel as a potential ER Ca(2+) leak channel and identified calmodulin as limiting Ca(2+) leakage in a Ca(2+)-dependent manner by binding to an IQ motif in the cytosolic aminoterminus of Sec61alpha. Here, we manipulated the concentration of the ER lumenal chaperone BiP in cells in different ways and used live cell Ca(2+) imaging to monitor the effects of reduced levels of BiP on ER Ca(2+) leakage. Regardless of how the BiP concentration was lowered, the absence of available BiP led to increased Ca(2+) leakage via the Sec61 complex. When we replaced wild-type Sec61alpha with mutant Sec61alphaY344H in the same model cell, however, Ca(2+) leakage from the ER increased and was no longer affected by manipulation of the BiP concentration. Thus, BiP limits ER Ca(2+) leakage through the Sec61 complex by binding to the ER lumenal loop 7 of Sec61alpha in the vicinity of tyrosine 344. |
