Theoretical considerations on the topological organization of receptor mosaics.
The concept of Receptor Mosaic (RM) is discussed; hence the integrative functions of the assemblage of G-protein coupled receptors physically interacting in the plane of the plasma membrane. The main focus is on a hetero-trimer of G-protein coupled receptors, namely the A2A-D2-CB1 receptor trimer. A bioinformatics analysis was carried out on the amino acid sequence of these receptors to indicate domains possibly involved in the receptor-receptor interactions. Such a bioinformatic analysis was also carried out on the RM formed by mGLU R5, D2 and A2A. The importance of topology, i.e., of the reciprocal localisation of the three interacting receptors in the plan of the membrane for the RM integrative functions is underlined. However, it is also pointed out that this fundamental aspect still waits techniques capable of an appropriate investigation. Finally, it is discussed how RM topology can give hints for a structural definition of the concept of hub receptor. Thus, just as in any network, the receptor operating as a hub is the one that in the molecular network formed by the receptors has the highest number of inputs.
Francesco
Agnati Luigi
AL
Department BioMedical Sciences, University of Modena and Reggio Emilia and IRCCS Lido, Venezia, Italy. luigiagnati@tin.it
Kjell
Fuxe
F
Amina
Woods
W
Susanna
Genedani
G
Diego
Guidolin
G
D000494:Allosteric Regulation; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D008565:Membrane Proteins; D021122:Protein Subunits; D043562:Receptors, G-Protein-Coupled