title: Inseparable tandem: evolution chooses ATP and Ca2+ to control life, death and cellular signalling.
abstract: From the very dawn of biological evolution, ATP was selected as a multipurpose energy-storing molecule. Metabolism of ATP required intracellular free Ca(2+) to be set at exceedingly low concentrations, which in turn provided the background for the role of Ca(2+) as a universal signalling molecule. The early-eukaryote life forms also evolved functional compartmentalization and vesicle trafficking, which used Ca(2+) as a universal signalling ion; similarly, Ca(2+) is needed for regulation of ciliary and flagellar beat, amoeboid movement, intracellular transport, as well as of numerous metabolic processes. Thus, during evolution, exploitation of atmospheric oxygen and increasingly efficient ATP production via oxidative phosphorylation by bacterial endosymbionts were a first step for the emergence of complex eukaryotic cells. Simultaneously, Ca(2+) started to be exploited for short-range signalling, despite restrictions by the preset phosphate-based energy metabolism, when both phosphates and Ca(2+) interfere with each other because of the low solubility of calcium phosphates. The need to keep cytosolic Ca(2+) low forced cells to restrict Ca(2+) signals in space and time and to develop energetically favourable Ca(2+) signalling and Ca(2+) microdomains. These steps in tandem dominated further evolution. The ATP molecule (often released by Ca(2+)-regulated exocytosis) rapidly grew to be the universal chemical messenger for intercellular communication; ATP effects are mediated by an extended family of purinoceptors often linked to Ca(2+) signalling. Similar to atmospheric oxygen, Ca(2+) must have been reverted from a deleterious agent to a most useful (intra- and extracellular) signalling molecule. Invention of intracellular trafficking further increased the role for Ca(2+) homeostasis that became critical for regulation of cell survival and cell death. Several mutually interdependent effects of Ca(2+) and ATP have been exploited in evolution, thus turning an originally unholy alliance into a fascinating success story.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'.
authors.affiliation: Department of Biology, University of Konstanz, 78457 Konstanz, Germany helmut.plattner@uni-konstanz.de.
authors.forename: Helmut
authors.identifier: 0000-0002-2594-5591
authors.initials: H
authors.lastname: Plattner
authors.affiliation: Faculty of Biological Sciences, University of Manchester, Manchester M13 9PT, UK Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain Department of Neurosciences, University of the Basque Country UPV/EHU and CIBERNED, Leioa, Spain University of Nizhny Novgorod, Nizhny Novgorod 603022, Russia alexej.verkhratsky@manchester.ac.uk.
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002450:Cell Communication; D005057:Eukaryotic Cells / Q000502:physiology*; D019143:Evolution, Molecular; D015398:Signal Transduction
chemical_list: D000255:Adenosine Triphosphate; D002118:Calcium
keywords: ATP; ATP receptors; Ca2+; calcium; evolution; intracellular organelles