The Heterogeneity of ER Ca²⁺ Stores Has a Key Role in Nonmuscle Cell Signaling and Function

The heterogeneity of the endoplasmic reticulum (ER) is well established in cell biology. To a large extent, however, the differences among ER domains (such as the nuclear envelope and the rough- and smooth-surfaced cisternae) are believed to reflect their different involvement in the synthesis, transport, and local degradation of proteins. In contrast, another function of the ER, i.e., its capacity to accumulate Ca²⁺ and to release it quickly in response to specific signals (see reference 32), is often regarded as a property of the whole network. Yet in striated muscles, the heterogeneity of Ca²⁺ handling in the sarcoplasmic reticulum (SR, a specialized version of the ER) was recognized over 20 yr ago. 10 yr later, based on pioneering subcellular fractionation and immunocytochemical results, a group of laboratories first proposed that structures specialized for Ca²⁺ handling, the calciosomes, may also exist in nonmuscle cells (...