Journal
JOURNAL OF CELL SCIENCE
Volume 126, Issue 17, Pages 3893-3903Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.125856
Keywords
Endoplasmic reticulum; Mitochondria; Quality control; Ca2+ signaling; ERp57; SERCA2b
Categories
Funding
- Alberta Cancer Foundation [25018, 24136, 25370]
- Canadian Cancer Society Research Institute [2010-700306]
- Alberta Innovates Health Solutions [200500396]
- Canadian Institutes of Health Research (CIHR) [NHG 99085]
- CIHR [MOP 81248]
- Alberta Cancer Research Institute (ACRI) [24425]
- Israel Science Foundation [1070/10]
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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) Ca2+ transport ATPase (SERCA) 2b and that this interaction determines ER Ca2+ content and the regulation of ER-mitochondria Ca2+ 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 Ca2+ 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 Ca2+ signaling or to protein chaperoning.
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