| First Author | Schwindinger WF | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 39 | Pages | 29787-96 |
| PubMed ID | 20639202 | Mgi Jnum | J:166391 |
| Mgi Id | MGI:4844225 | Doi | 10.1074/jbc.M110.142620 |
| Citation | Schwindinger WF, et al. (2010) Adenosine A2A receptor signaling and golf assembly show a specific requirement for the gamma7 subtype in the striatum. J Biol Chem 285(39):29787-96 |
| abstractText | The adenosine A(2A) receptor (A(2A)R) is increasingly recognized as a novel therapeutic target in Parkinson disease. In striatopallidal neurons, the G-protein alpha(olf) subtype is required to couple this receptor to adenylyl cyclase activation. It is now well established that the betagamma dimer also performs an active role in this signal transduction process. In principal, sixty distinct betagamma dimers could arise from combinatorial association of the five known beta and 12 gamma subunit genes. However, key questions regarding which betagamma subunit combinations exist and whether they perform specific signaling roles in the context of the organism remain to be answered. To explore these questions, we used a gene targeting approach to specifically ablate the G-protein gamma(7) subtype. Revealing a potentially new signaling paradigm, we show that the level of the gamma(7) protein controls the hierarchial assembly of a specific G-protein alpha(olf)beta(2)gamma(7) heterotrimer in the striatum. Providing a probable basis for the selectivity of receptor signaling, we further demonstrate that loss of this specific G-protein heterotrimer leads to reduced A(2A)R activation of adenylyl cyclase. Finally, substantiating an important role for this signaling pathway in pyschostimulant responsiveness, we show that mice lacking the G-protein gamma(7) subtype exhibit an attenuated behavioral response to caffeine. Collectively, these results further support the A(2A)R G-protein alpha(olf)beta(2)gamma(7) interface as a possible therapeutic target for Parkinson disease. |
