Title:Purinergic Signalling: What is Missing and Needed Next? The Use of Transgenic Mice, Crystallographic Analysis and MicroRNA
Volume: 11
Issue: 6
Author(s): C. Volonte, C. Parisi and G. Burnstock
Affiliation:
Keywords:
Ectonucleotidases, extracellular adenosine, extracellular ATP, nervous system, purinergic signalling, purinergic
receptors, Argonaute, Brain Derived Neurotrophic Factor, Central Nervous System, Tumor Necrosis Factor-alpha
Abstract: While ATP is recognized as an intracellular energy source for many biochemical reactions, it is now recognised
it is also an important extracellular signalling molecule. ATP is involved in both physiological and pathological events in
most cell types, and receptor subtypes have been cloned and characterised. An important goal of purinergic research today
is to annotate the human genome with functional information regarding the role of genes for purinergic receptors,
ectonucleotidases and transporters, in brain physiology and pathology. Insights into these roles have been gained also
from studies of the various purinergic knockouts, and here we report on the generation of these purinergic
receptor/ectonucleotidase-null mice. Recent X-ray structures of purinergic ligand-activated receptors provide promising
templates to understand the molecular mechanism of receptor actions at the atomic level, and to deploy X-ray structures to
be used for structure-based drug design. In the present work we also summarize recent findings about X-ray structures of
ionotropic and metabotropic purinergic receptors and ectonucleotidases. A novel and prominent role as modulators of
signal propagation in animal cells is played by microRNAs. By acting as genetic switches, they might become stringent
regulators of the variety of cellular responses triggered by the dynamic interactions between purinergic receptors,
nucleotides/nucleosides, transporters and ectonucleotidases. In this review we highlight data on the regulation of
purinergic mechanisms by microRNAs. Finally, we would like to illustrate what information is still missing or needed for
the acquisition of a more complete knowledge of purinergic signalling.
