University of Adelaide Library

Adelaide Research and Scholarship : Schools and Disciplines : School of Molecular and Biomedical Science : Microbiology and Immunology : Microbiology and Immunology publications

Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/74387

Type: Journal article
Title: BiP-mediated closing of the Sec61 channel limits Ca²⁺ leakage from the ER
Other Titles: BiP-mediated closing of the Sec61 channel limits Ca(2+) leakage from the ER
Author: Schauble, N.
Lang, S.
Jung, M.
Cappel, S.
Schorr, S.
Ulucan, O.
Linxweiler, J.
Dudek, J.
Blum, R.
Helms, V.
Paton, A.
Paton, J.
Cavalie, A.
Zimmerman, R.
Citation: EMBO Journal, 2012; 31(15):3282-3296
Publisher: Nature Publishing Group
Issue Date: 2012
ISSN: 0261-4189
1460-2075
Statement of
Responsibility: 
Nico Schäuble, Sven Lang, Martin Jung, Sabine Cappel, Stefan Schorr, Özlem Ulucan, Johannes Linxweiler, Johanna Dudek, Robert Blum, Volkhard Helms, Adrienne W Paton, James C Paton, Adolfo Cavalié and Richard Zimmermann
Abstract: 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 Ca²⁺ leak channel and identified calmodulin as limiting Ca²⁺ leakage in a Ca²⁺-dependent manner by binding to an IQ motif in the cytosolic aminoterminus of Sec61α. Here, we manipulated the concentration of the ER lumenal chaperone BiP in cells in different ways and used live cell Ca²⁺ imaging to monitor the effects of reduced levels of BiP on ER Ca²⁺ leakage. Regardless of how the BiP concentration was lowered, the absence of available BiP led to increased Ca²⁺ leakage via the Sec61 complex. When we replaced wild-type Sec61α with mutant Sec61αY344H in the same model cell, however, Ca²⁺ leakage from the ER increased and was no longer affected by manipulation of the BiP concentration. Thus, BiP limits ER Ca²⁺ leakage through the Sec61 complex by binding to the ER lumenal loop 7 of Sec61α in the vicinity of tyrosine 344.
Keywords: BiP; calcium homeostasis; diabetes mutation; endoplasmic reticulum; ER calcium leakage; Sec61 complex gating
Rights: ©2012 European Molecular Biology Organization
RMID: 0020121429
DOI: 10.1038/emboj.2012.189
Appears in Collections:Microbiology and Immunology publications
View citing articles in: Web of Science
Google Scholar
Scopus

There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

© 2008 The University of Adelaide
library@adelaide.edu.au
CRICOS Provider Number 00123M
Service Charter | Copyright | Privacy | Disclaimer