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.
| Original language | English |
|---|---|
| Pages (from-to) | 751-767 |
| Number of pages | 17 |
| Journal | CNS and Neurological Disorders - Drug Targets |
| Volume | 11 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2012 |
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Keywords
- Ectonucleotidases
- Extracellular adenosine
- Extracellular ATP
- Nervous system
- Purinergic receptors
- Purinergic signalling
ASJC Scopus subject areas
- Neuroscience(all)
- Pharmacology
Cite this
Purinergic signalling : What is missing and needed next? The use of transgenic mice, crystallographic analysis and microRNA. / Volonté, C.; Parisi, C.; Burnstock, G.
In: CNS and Neurological Disorders - Drug Targets, Vol. 11, No. 6, 2012, p. 751-767.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Purinergic signalling
T2 - What is missing and needed next? The use of transgenic mice, crystallographic analysis and microRNA
AU - Volonté, C.
AU - Parisi, C.
AU - Burnstock, G.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Ectonucleotidases
KW - Extracellular adenosine
KW - Extracellular ATP
KW - Nervous system
KW - Purinergic receptors
KW - Purinergic signalling
UR - http://www.scopus.com/inward/record.url?scp=84869014228&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869014228&partnerID=8YFLogxK
U2 - 10.2174/187152712803581146
DO - 10.2174/187152712803581146
M3 - Article
C2 - 22963439
AN - SCOPUS:84869014228
VL - 11
SP - 751
EP - 767
JO - CNS and Neurological Disorders - Drug Targets
JF - CNS and Neurological Disorders - Drug Targets
SN - 1871-5273
IS - 6
ER -