Ca2+ tunnelling through the ER lumen as a mechanism for delivering Ca2+ entering via store-operated Ca2+ channels to specific target sites.

Overview

Ca²⁺ 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 Ca²⁺ concentration. In electrically non-excitable cells, for example epithelial cells, this is achieved by primary release of Ca²⁺ from the endoplasmic reticulum via Ca²⁺ release channels placed close to the physiological target. Because any rise in the cytosolic Ca²⁺ concentration activates Ca²⁺ extrusion, and in order for cells not to run out of Ca²⁺ , there is a need for compensatory Ca²⁺ uptake from the extracellular fluid. This Ca²⁺ uptake occurs through a process known as store-operated Ca²⁺ entry. Ideally Ca²⁺ entering the cell should not diffuse to the target site through the cytosol, as this would potentially activate undesirable processes. Ca²⁺ tunnelling through the lumen of the endoplasmic reticulum is a mechanism for delivering Ca²⁺ entering via store-operated Ca²⁺ 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.