Ca2+ signalling early in evolution--all but primitive.

Early in evolution, Ca(2+) emerged as the most important second messenger for regulating widely different cellular functions. In eukaryotic cells Ca(2+) signals originate from several sources, i.e. influx from the outside medium, release from internal stores or from both. In mammalian cells, Ca(2+)-release channels represented by inositol 1,4,5-trisphosphate receptors and ryanodine receptors (InsP3R and RyR, respectively) are the most important. In unicellular organisms and plants, these channels are characterised with much less precision. In the ciliated protozoan, Paramecium tetraurelia, 34 molecularly distinct Ca(2+)-release channels that can be grouped in six subfamilies, based on criteria such as domain structure, pore, selectivity filter and activation mechanism have been identified. Some of these channels are genuine InsP3Rs and some are related to RyRs. Others show some--but not all--features that are characteristic for one or the other type of release channel. Localisation and gene silencing experiments revealed widely different--yet distinct--localisation, activation and functional engagement of the different Ca(2+)-release channels. Here, we shall discuss early evolutionary routes of Ca(2+)-release machinery in protozoa and demonstrate that detailed domain analyses and scrutinised functional analyses are instrumental for in-depth evolutionary mapping of Ca(2+)-release channels in unicellular organisms.