GTP-Mediated Communication Between Intracellular Calcium Pools

Abstract

The release of intracellular Ca²⁺ is widely established as a major component of receptor-mediated cytosolic Ca²⁺ signals (Gill et al. 1989; Berridge 1990; Berridge and Irvine 1989). Yet the nature and location of Ca²⁺ pools from which Ca²⁺ is released remain poorly characterized. There is good evidence that the endoplasmic reticulum (ER) is an important Ca²⁺-sequestering site within cells and a probable major target for the intracellular mediator of Ca²⁺ release, inositol 1,4,5-trisphosphate (InsP₃) (Ghosh et al. 1989). However, the ER itself constitutes a large and heterogeneous organelle in most cells; obvious subdomains of the ER exist, including rough and smooth cisternae and the nuclear envelope. In addition, it is likely that microheterogeneity of ER results in subcompartments of ER that may have quite different properties, even though they are not morphologically distinguishable. For example, smooth cisternae are widely distributed in cells; some deep within the cell, others sometimes close to the plasma membrane. It is very possible that different Ca²⁺ handling properties are associated with ER at different locations. This does not necessarily imply that there are distinct Ca²⁺ transport mechanisms at such locations. Instead, differences may arise, for example, in proximity of ER cisternae to the plasma membrane, those closest receiving the most rapid exposure to the highest concentrations of InsP₃. Others believe that organelles perhaps closely associated with, but distinct from, ER may represent the major Ca²⁺-signaling pools. Such organelles were termed “calciosomes” by Meldolesi and colleagues (Volpe et al. 1988). This view has been based on a number of observations including the immunocytochemical localization of Ca²⁺-binding proteins, Ca²⁺ pumps, and InsP₃ receptors. However, as yet there does not seem to be overwhelming evidence for a clearly identifiable and discrete Ca²⁺-signaling organelle (Rossier and Putney 1991). Thus, whereas it may be reasonable to refer to the source of Ca²⁺ releasable by InsP₃ as “calciosomes”, it is clear that we have no defined idea of what such organelles are or whether they are distinct from the ER.