An integrated view on the role of receptor mosaics at perisynaptic level: focus on adenosine A(2A), dopamine D(2), cannabinoid CB(1), and metabotropic glutamate mGlu(5) receptors.
The available evidence for receptor-receptor interactions between adenosine A(2A), dopamine D(2), cannabinoid CB(1), and metabotropic glutamate mGlu(5) receptors (A(2A), D(2), CB(1), and mGlu(5), respectively) is revised under the "receptor mosaic" perspective. Furthermore, the concept of "hub receptor" is defined in accordance with informatics and it is tentatively illustrated in the case of the hypothesized tetramer formed by the above mentioned receptors. On the basis of some biochemical features of the four receptors and of a bioinformatics analysis, an objective deduction of their "similarity" has been obtained. To this aim the Canberra, Euclidean and Chebyshev multivariate distance metrics have been used. It is interesting to note that A(2A) and D(2) are the most different ones, while CB(1) and mGlu(5) are the most similar ones among the four receptors analyzed. Finally, by means of a bioinformatics analysis based on different approaches the possible binding sites mediating G-protein-coupled receptor (GPCR) interactions have been indicated. It is interesting to note that in some instances accordance has been found between the bioinformatics indications and the available experimental data.
Agnati
Luigi F
LF
IRCCS San Camillo, Lido Venezia, Italy. luigiagnati@tin.it
Guidolin
Diego
D
Albertin
Giovanna
G
Trivello
Elena
E
Ciruela
Francisco
F
Genedani
Susanna
S
Tarakanov
Alexander
A
Fuxe
Kjell
K
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology / Q000379:methods; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D055503:Protein Multimerization; D043705:Receptor, Adenosine A2A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
D043705:Receptor, Adenosine A2A; D064529:Receptor, Metabotropic Glutamate 5; D017448:Receptors, Dopamine D2; D018094:Receptors, Metabotropic Glutamate