Regulation of calcium homeostasis and flux between the endoplasmic reticulum and the cytosol |
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Authors: | Lea Daverkausen-Fischer Felicitas Prls |
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Institution: | University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Anatomy II, Cologne, Germany |
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Abstract: | The concentration of Ca2+ in the endoplasmic reticulum (ER) is critically important for maintaining its oxidizing environment as well as for maintaining luminal ATP levels required for chaperone activity. Therefore, local luminal Ca2+ concentrations and the dynamic Ca2+ flux between the different subcellular compartments are tightly controlled. Influx of Ca2+ into the ER is enabled by a reductive shift, which opens the sarcoendoplasmic reticulum calcium transport ATPase pump, building the Ca2+ gradient across the ER membrane required for ATP import. Meanwhile, Ca2+ leakage from the ER has been reported to occur via the Sec61 translocon following protein translocation. In this review, we provide an overview of the complex regulation of Ca2+ homeostasis, Ca2+ flux between subcellular compartments, and the cellular stress response (the unfolded protein response) induced upon dysregulated luminal Ca2+ metabolism. We also provide insight into the structure and gating mechanism at the Sec61 translocon and examine the role of ER-resident cochaperones in assisting the central ER-resident chaperone BiP in the control of luminal Ca2+ concentrations. |
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Keywords: | translocon chaperone J-proteins DnaJ thioredoxin stress BiP/Grp78/HspA5 diabetes UPR |
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