Extracellular adenosine is a ubiquitous signaling molecule that modulates many physiological processes. Its actions are mediated by interaction with four subtypes of adenosine receptors, A1, A2A, A2B and A3. We found that two mutations in the C-terminus of A2B adenosine receptors, F298A and R299A, substantially impaired the protein expression of A2B adenosine receptors, although the transcriptions of the two mutants seemed normal. We speculated that these two mutations destabilized the protein probably by disrupting interaction of A2B adenosine receptor with a protein(s) that is essential for the stability of A2B adenosine receptor. We show that alpha-actinin-1, an actin-associated protein, interacts with the C-terminus of A2B adenosine receptors and stabilize its expression in the cell...[ Read more ]

Extracellular adenosine is a ubiquitous signaling molecule that modulates many physiological processes. Its actions are mediated by interaction with four subtypes of adenosine receptors, A1, A2A, A2B and A3. We found that two mutations in the C-terminus of A2B adenosine receptors, F298A and R299A, substantially impaired the protein expression of A2B adenosine receptors, although the transcriptions of the two mutants seemed normal. We speculated that these two mutations destabilized the protein probably by disrupting interaction of A2B adenosine receptor with a protein(s) that is essential for the stability of A2B adenosine receptor. We show that alpha-actinin-1, an actin-associated protein, interacts with the C-terminus of A2B adenosine receptors and stabilize its expression in the cell. In contrast, alpha-actinin-4, another non-muscle isoform of alpha-actinins, did not interact with A2B adenosine receptor. Moreover, the mutations of F298A and R299A disrupted A2B receptors’ interaction with alpha-actinin-1. Our results reveal a novel regulator mechanism for the expression of A2B adenosine receptor.