The ancient roots of calcium signalling evolutionary tree

Abstract

Molecular cascades of calcium homeostasis and signalling (Ca²⁺ pumps, channels, cation exchangers, and Ca²⁺-binding proteins) emerged in prokaryotes and further developed at the unicellular stage of eukaryote evolution. With progressive evolution, mechanisms of signalling became diversified reflecting multiplication and specialisation of Ca²⁺-regulated cellular activities. Recent genomic analysis of organisms from different systematic positions, combined with proteomic and functional probing invigorated expansion in our understanding of the evolution of Ca²⁺ signalling. Particularly impressive is the consistent role of Ca²⁺-ATPases/pumps, calmodulin and calcineurin from very early stages of eukaryotic evolution, although with interspecies differences. Deviations in Ca²⁺ handling and signalling are observed between vertebrates and flowering plants as well as between protists at the basis of the two systematic categories, Unikonta (for example choanoflagellates) and Bikonta (for example ciliates). Only the B-subunit of calcineurin, for instance, is maintained to regulate highly diversified protein kinases for stress defence in flowering plants, whereas the complete dimeric protein, in vertebrates up to humans, regulates gene transcription, immune-defence and plasticity of the brain. Calmodulin is similarly maintained throughout evolution, but in plants a calmoldulin-like domain is integrated into protein kinase molecules. The eukaryotic cell has inherited and invented many mechanisms to exploit the advantages of signalling by Ca²⁺, and there is considerable overall similarity in basic processes of Ca²⁺ regulation and signalling during evolution, although some details may vary.