- Meeting abstract
- Open Access
Receptor G protein coupling and the cytoskeleton
© Charalambous et al; licensee BioMed Central Ltd. 2007
- Published: 14 November 2007
- Adenylyl Cyclase
- Adenosine Receptor
- Striatal Neuron
- Fluorescence Recovery
- Restricted Mobility
The A2A adenosine receptor is a prototypical Gs protein-coupled receptor; it has been proposed as a drug target in the treatment of Parkinson's disease, because there is a mutual antagonism between D2 dopamine and A2A receptors in striatal neurons. Because of their ability to stimulate endothelial cell proliferation, A2A agonists are in clinical development for diabetic ulcers. Several modes of coupling have been proposed to account for the interaction of receptor and G proteins; these have been termed precoupling, restricted collision coupling etc. Here, we investigated the mode of coupling of the A2A receptor by visualizing agonist-induced changes in mobility of the YFP-tagged receptor by FRAP (fluorescence recovery after photobleaching) microscopy. Agonist stimulation did not affect the mobility of the A2A receptor; in contrast, agonist challenge induced a decrease in the mobility of the D2 receptor. When coexpressed in the same cell, the A2A receptor precluded the agonist-induced change in D2 receptor mobility. Thus, the A2A receptor does not only undergo restricted collision coupling but it also restricts the mobility of the D2 receptor. Restricted mobility is not due to tethering to the actin cytoskeleton but is, in part, related to the cholesterol content of the membrane. Depletion of cholesterol increases receptor mobility, but blunts activation of adenylyl cyclase. We conclude that signalling of the A2A receptor takes place in cholesterol-rich domains of the membrane.
This article is published under license to BioMed Central Ltd.