Molecular aspects of calcium signalling at the crossroads of unikont and bikont eukaryote evolution – The ciliated protozoan Paramecium in focus

Abstract

The ciliated protozoan, Paramecium tetraurelia has a high basic Ca(2+) leakage rate which is counteracted mainly by export through a contractile vacuole complex, based on its V-type H(+)-ATPase activity. In addition Paramecium cells dispose of P-type Ca(2+)-ATPases, i.e. a plasmamembrane and a sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (PMCA, SERCA). Antiporter systems are to be expected, as inferred from indirect evidence. Among the best known cytosolic Ca(2+)-binding proteins, calmodulin activates Ca(2+) influx channels in the somatic cell membrane, but inactivates Ca(2+) influx channels in cilia, where it, thus, ends ciliary reversal induced by depolarization via channels in the somatic cell membrane. Centrin inactivates Ca(2+) signals after stimulation by its high capacity/low affinity binding sites, whereas its high affinity sites regulate some other functions. Cortical Ca(2+) stores (alveolar sacs) are activated during stimulated trichocyst exocytosis and thereby mediate store-operated Ca(2+) entry (SOCE). Ca(2+) release channels (CRCs) localised to alveoli and underlying SOCE are considered as Ryanodine receptor-like proteins (RyR-LPs) which are members of a CRC family with 6 subfamilies. These also encompass genuine inositol 1,4,5-trisphosphate receptors (IP3Rs) and intermediates between the two channel types. All IP3R/RyR-type CRCs possess six carboxyterminal transmembrane domains (TMD), with a pore domain between TMD 5 and 6, endowed with a characteristic selectivity filter. There are reasons to assume a common ancestor molecule for such channels and diversification further on in evolution. The distinct distribution of specific CRCs in the different vesicles undergoing intracellular trafficking suggests constitutive formation of very locally restricted Ca(2+) signals during vesicle-vesicle interaction. In summary, essential steps of Ca(2+) signalling already occur at this level of evolution, including an unexpected multitude of CRCs. For dis-/similarities with other bikonts see "Conclusions".

Inseparable tandem: evolution chooses ATP and Ca2+to control life, death and cellular signalling

“…The signal may come from the very same trafficking organelles, as they contain Ca 2þ -release channels of different types, including InsP 3 Rs and RyRs. This is true from protozoa [38,88] to mammals [98], even though other types of Ca 2þ -release channels can also be involved (not considered here). Organelles of the endophagocytotic/lysosomal pathway contain Ca 2þ at different concentrations [138]; release of Ca 2þ drives local vesicle-vesicle interactions and fusion.…”

“…Nonetheless, Ca 2þ permeation through biomembranes, though variable and tightly controlled, is unavoidable. Like with oxygen which, when emerging in the atmosphere instigated the extinction of almost all living forms, evolution turned a disadvantage into an advantage by taming toxicity through spatial and temporal restriction [25,38,39]. Ionized Ca 2þ has to be kept low in the cytosol to avoid interference with phosphate groups in free and bound form.…”

“…H þ /Ca 2þ exchangers or related antiporters), all to be found in the plasmalemma and in the endomembranes [20,22,76,77]; intracellular Ca 2þ dynamics is further regulated by Ca 2þ buffers [56]. All these mechanisms were invented early in evolution, be it in ancestors of unikonts, such as choanoflagellates [78], or be it in bikonts, such as ciliates [38,40]. Cytosol contains both mobile and immobile Ca 2þ buffers of different capacity and affinity.…”

“…In conclusion, there are diverse ways to release Ca 2þ locally by different activators, only some being considered here. Considerable similarities between InsP 3 Rs and RyRs from ciliated protozoa [88] to mammals [98] indicate that both may possibly have evolved from a common ancestral molecule, assembled from six transmembrane domains [38,89].…”

“…Although operational SOCE is well characterized in the ciliate, Paramecium [40], Orai and Stim have not been detected (as yet), in contrast to informatics data obtained from choanoflagellates [78] that are placed at the basis of metazoans. However, several alternative modes of cell membranecortical store coupling are discussed, for instance by extended synaptotagmins with super-numerary C2 domains [133] which also occur in ciliates [38]. Altogether, SOCE appears to be an evolutionarily old mechanism.…”