Adenosine A2A receptor signaling and golf assembly show a specific requirement for the gamma7 subtype in the striatum.

The Journal of Biological Chemistry
William F SchwindingerJanet D Robishaw

Abstract

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 α(olf) subtype is required to couple this receptor to adenylyl cyclase activation. It is now well established that the βγ dimer also performs an active role in this signal transduction process. In principal, sixty distinct βγ dimers could arise from combinatorial association of the five known β and 12 γ subunit genes. However, key questions regarding which βγ 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 γ(7) subtype. Revealing a potentially new signaling paradigm, we show that the level of the γ(7) protein controls the hierarchial assembly of a specific G-protein α(olf)β(2)γ(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 r...Continue Reading

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Citations

Dec 31, 2011·The Journal of Biological Chemistry·William F SchwindingerJanet D Robishaw
Oct 23, 2013·The Journal of Experimental Medicine·Caglar CekicJoel Linden
Mar 7, 2014·PloS One·Anne M MoonJanet D Robishaw
Feb 27, 2014·Biochemistry·Katherine M BetkeHeidi E Hamm
Oct 25, 2016·Frontiers in Cellular Neuroscience·Csaba VastaghZsolt Liposits
Oct 19, 2017·The Journal of Biological Chemistry·Hideaki YanoJonathan A Javitch
Feb 3, 2019·The Journal of Biological Chemistry·Zack ZurawskiHeidi E Hamm
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Jan 11, 2018·The Journal of Biological Chemistry·Kanishka SenarathAjith Karunarathne
Feb 15, 2021·Cellular Signalling·Mithila TennakoonAjith Karunarathne
Mar 6, 2021·Cell Systems·Ikuo MasuhoKirill A Martemyanov
Sep 5, 2021·Pharmacology & Therapeutics·Sergi FerréLeonardo Pardo

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