The regulation of a cell's Ca(2+) signaling toolkit: the Ca (2+) homeostasome

The Ca(2+) ion serves as a ubiquitous second messenger in eukaryotic cells and changes in the intracellular Ca(2+) concentration regulate many responses within a cell, but also communication between cells. In order to make use of such an apparently simple signal, i.e. a change in the intracellular Ca(2+) concentration, cells are equipped with sophisticated machinery to precisely regulate the shape (amplitude, duration) of Ca(2+) signals in a localization-specific manner. To ascertain such a precise regulation, cells rely on the components of the Ca(2+) signaling toolkit. This embraces Ca(2+) entry systems including Ca(2+) channels in the plasma membrane and organellar membranes, and Ca(2+) extrusion/uptake systems including Ca(2+)-ATPases (Ca(2+) pumps) and Na(+)/Ca(2+) exchangers. Besides mitochondria, organelles implicated also in Ca(2+) signaling, cytosolic Ca(2+) buffers are cell-specific subtle modulators of Ca(2+) signals. The Ca(2+)-signaling components not only orchestrate their activity as to ascertain the high accuracy of intracellular Ca(2+) signaling, but they are also implicated in the regulation of their own expression. The total of the molecules that build the network of Ca(2+) signaling components, and that are involved in their own regulation as to maintain physiological Ca(2+) homeostasis resulting in phenotypic stability is named the Ca(2+) homeostasome. Mechanistic details on the functioning of the Ca(2+) homeostasome are presented.