Evolutionary origins of the purinergic signalling system

Abstract

Purines appear to be the most primitive and widespread chemical messengers in the animal and plant kingdoms. The evidence for purinergic signalling in plants, invertebrates and lower vertebrates is reviewed. Much is based on pharmacological studies, but important recent studies have utilized the techniques of molecular biology and receptors have been cloned and characterized in primitive invertebrates, including the social amoeba Dictyostelium and the platyhelminth Schistosoma, as well as the green algae Ostreococcus, which resemble P2X receptors identified in mammals. This suggests that contrary to earlier speculations, P2X ion channel receptors appeared early in evolution, while G protein-coupled P1 and P2Y receptors were introduced either at the same time or perhaps even later. The absence of gene coding for P2X receptors in some animal groups [e.g. in some insects, roundworms (Caenorhabditis elegans) and the plant Arabidopsis] in contrast to the potent pharmacological actions of nucleotides in the same species, suggests that novel receptors are still to be discovered.

Cellular function and molecular structure of ecto-nucleotidases

“…Interestingly, these enzymes are missing in the Drosophila and Caenorhabditis elegans genome. The apparent lack of P2X receptors in these organisms [187] further supports the notion that expression of ecto-NTPDases is a hallmark of purinergic signaling. In contrast, members of the protein family relating to the intracellular forms are present throughout the animal kingdom and also in plants and fungi [37,188].…”

Purinergic control of lysenin’s transport and voltage-gating properties

“…Purinergic signaling, broadly defined as modulation of shortterm and long-term signaling functions presented by purines and pyrimidines [1,2], is widely recognized as a fundamental mechanism of control at the molecular and cellular level in all kingdoms of life [3,4]. Neurotransmission, secretion, transduction, cell proliferation, motility, and differentiation are typical examples of biological functions modulated by nucleotides or nucleosides acting as extracellular signaling molecules [5][6][7][8][9][10][11].…”

“…protein-coupled P2Y receptors [1,3,19,21,[23][24][25][26][27][28]. Although multiple past studies focused on understanding the implications of ATP-controlled signaling with respect to endogenous transmembrane transporters such as ion channels [17,19,20,24,[28][29][30][31], there is a recent interest in understanding how ATP controls the lytic action of pore-forming toxins (PFTs) [22,26,27,[32][33][34].…”

The touching story of purinergic signaling in epithelial and endothelial cells

“…With an impressive number of molecular members of the system (15 P2 receptor subtypes and in total 16 nucleotide-degrading enzymes), cells have managed to put purines and pyrimidines as well as their derivatives to use in an array of different areas, including regulation of flow, secretion, and vascular tone. Indeed, the purinergic signaling system is an ancient way of intercellular communication that most likely could be found in the first most primitive life form [1]. The scope of this review is to give an overview of exciting features of purinergic signaling and examples of gaps to fill in understanding its role in the cells lining the body-the endothelium and the epithelium.…”