Ca2+ signalling early in evolution - all but primitive

Early in evolution, Ca2+ emerged as the most important second messenger for regulating widely different cellular functions. In eukaryotic cells Ca2+ signals originate from several sources, i.e. influx from the outside medium, release from internal stores or from both. In mammalian cells, Ca2+-release channels represented by inositol 1,4,5-trisphosphate receptors and ryanodine receptors (InsP(3)R 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 Ca2+-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 InsP(3)Rs 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 Ca2+-release channels. Here, we shall discuss early evolutionary routes of Ca2+-release machinery in protozoa and demonstrate that detailed domain analyses and scrutinised functional analyses are instrumental for in-depth evolutionary mapping of Ca2+-release channels in unicellular organisms.