The A(2A)-adenosine receptor: a GPCR with unique features?
The A(2A)-adenosine receptor is a prototypical G(s)-coupled receptor. However, the A(2A)-receptor has several structural and functional characteristics that make it unique. In contrast to the classical model of collision coupling described for the beta-adrenergic receptors, the A(2A)-receptor couples to adenylyl cyclase by restricted collision coupling and forms a tight complex with G(s). The mechanistic basis for this is not clear; restricted collision coupling may arise from the interaction of the receptor with additional proteins or due to the fact that G protein-coupling is confined to specialized membrane microdomains. The A(2A)-receptor has a long C-terminus (of >120 residues), which is for the most part dispensable for coupling to G(s). It was originally viewed as the docking site for kinases and the beta-arrestin family to initiate receptor desensitization and endocytosis. The A(2A)-receptor is, however, fairly resistant to agonist-induced internalization. Recently, the C-terminus has also been appreciated as a binding site for several additional 'accessory' proteins. Established interaction partners include alpha-actinin, ARNO, USP4 and translin-associated protein-X. In addition, the A(2A)-receptor has also been reported to form a heteromeric complex with the D(2)-dopamine receptor and the metabotropic glutamate receptor-5. It is clear that (i) this list cannot be exhaustive and (ii) that all these proteins cannot bind simultaneously to the receptor. There must be rules of engagement, which allow the receptor to elicit different biological responses, which depend on the cellular context and the nature of the concomitant signal(s). Thus, the receptor may function as a coincidence detector and a signal integrator.
Zezula
J
J
Center of Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Austria.
Freissmuth
M
M
D020727:ADP-Ribosylation Factors / Q000378:metabolism / Q000502:physiology; D000818:Animals; D020690:GTPase-Activating Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
D020690:GTPase-Activating Proteins; D043705:Receptor, Adenosine A2A; D043562:Receptors, G-Protein-Coupled; C102474:cytohesin-2; D020727:ADP-Ribosylation Factors