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BiP‐mediated closing of the Sec61 channel limits Ca 2+ leakage from the ER
Author(s) -
Schäuble Nico,
Lang Sven,
Jung Martin,
Cappel Sabine,
Schorr Stefan,
Ulucan Özlem,
Linxweiler Johannes,
Dudek Johanna,
Blum Robert,
Helms Volkhard,
Paton Adrienne W,
Paton James C,
Cavalié Adolfo,
Zimmermann Richard
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.189
Subject(s) - biology , leakage (economics) , closing (real estate) , biophysics , macroeconomics , political science , law , economics
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 Sec61α. 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 Sec61α with mutant Sec61αY344H 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 Sec61α in the vicinity of tyrosine 344.