Ca(2+) tunnelling through the ER lumen as a mechanism for delivering Ca(2+) entering via store‐operated Ca(2+) channels to specific target sites

Ca(2+) signalling is perhaps the most universal and versatile mechanism regulating a wide range of cellular processes. Because of the many different calcium‐binding proteins distributed throughout cells, signalling precision requires localized rises in the cytosolic Ca(2+) concentration. In electrically non‐excitable cells, for example epithelial cells, this is achieved by primary release of Ca(2+) from the endoplasmic reticulum via Ca(2+) release channels placed close to the physiological target. Because any rise in the cytosolic Ca(2+) concentration activates Ca(2+) extrusion, and in order for cells not to run out of Ca(2+), there is a need for compensatory Ca(2+) uptake from the extracellular fluid. This Ca(2+) uptake occurs through a process known as store‐operated Ca(2+) entry. Ideally Ca(2+) entering the cell should not diffuse to the target site through the cytosol, as this would potentially activate undesirable processes. Ca(2+) tunnelling through the lumen of the endoplasmic reticulum is a mechanism for delivering Ca(2+) entering via store‐operated Ca(2+) channels to specific target sites, and this process has been described in considerable detail in pancreatic acinar cells and oocytes. Here we review the most important evidence and present a generalized concept. [Image: see text]