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TitlePalmitoylation is the switch that assigns calnexin to quality control or ER Ca2+ signaling.
Publication TypeJournal Article
Year of Publication2013
AuthorsLynes, Emily M., Arun Raturi, Marina Shenkman, Carolina Ortiz Sandoval, Megan C. Yap, Jiahui Wu, Aleksandra Janowicz, Nathan Myhill, Matthew D. Benson, Robert E. Campbell, Luc G. Berthiaume, Gerardo Z. Lederkremer, and Thomas Simmen
JournalJ Cell Sci
IssuePt 17
Date Published2013 Sep 1
Keywords3T3 Cells, Animals, Calcium, Calcium Signaling, Calnexin, Cell Line, Endoplasmic Reticulum, Endoplasmic Reticulum Stress, Fibroblasts, HEK293 Cells, HeLa Cells, Humans, Lipoylation, Mice, Mitochondria, Mitochondrial Membranes, Protein Disulfide-Isomerases, Sarcoplasmic Reticulum Calcium-Transporting ATPases

The palmitoylation of calnexin serves to enrich calnexin on the mitochondria-associated membrane (MAM). Given a lack of information on the significance of this finding, we have investigated how this endoplasmic reticulum (ER)-internal sorting signal affects the functions of calnexin. Our results demonstrate that palmitoylated calnexin interacts with sarcoendoplasmic reticulum (SR) Ca(2+) transport ATPase (SERCA) 2b and that this interaction determines ER Ca(2+) content and the regulation of ER-mitochondria Ca(2+) crosstalk. In contrast, non-palmitoylated calnexin interacts with the oxidoreductase ERp57 and performs its well-known function in quality control. Interestingly, our results also show that calnexin palmitoylation is an ER-stress-dependent mechanism. Following a short-term ER stress, calnexin quickly becomes less palmitoylated, which shifts its function from the regulation of Ca(2+) signaling towards chaperoning and quality control of known substrates. These changes also correlate with a preferential distribution of calnexin to the MAM under resting conditions, or the rough ER and ER quality control compartment (ERQC) following ER stress. Our results have therefore identified the switch that assigns calnexin either to Ca(2+) signaling or to protein chaperoning.

Alternate JournalJ. Cell. Sci.
PubMed ID23843619
Grant ListMOP 81248 / / Canadian Institutes of Health Research / Canada
NHG 99085 / / Canadian Institutes of Health Research / Canada