G beta-gamma complex
When a G protein-coupled receptor (GPCR) is activated, Gα dissociates from Gβγ, allowing both subunits to perform their respective downstream signaling effects.
[1] The individual subunits of the G protein complex were first identified in 1980 when the regulatory component of adenylate cyclase was successfully purified, yielding three polypeptides of different molecular weights.
[3] Shortly after, the Gβγ complex associated with a mating factor receptor-coupled G protein in yeast was found to initiate a pheromone response.
[4] Although these hypotheses were initially controversial, Gβγ has since been shown to directly regulate as many different protein targets as the Gα subunit.
[1] Recently, possible roles of the Gβγ complex in retinal rod photoreceptors have been investigated, with some evidence for the maintenance of Gα inactivation.
However, these conclusions were drawn from in vitro experiments under unphysiological conditions, and the physiological role of the Gβγ complex in vision is still unclear.
Nevertheless, recent in vivo findings demonstrate the necessity of the transducin Gβγ complex in the functioning of rod photoreceptors under low light conditions.
[6] The Gβ subunit is a member of the β-propeller family of proteins, which typically possess four to eight antiparallel β-sheets arranged in the shape of a propeller.
In the heterotrimer form, the Gβγ dimer increases the affinity of Gα for GDP, which causes the G protein to be in an inactive state.
[19] Another example of Gβγ signaling is its effect of activating or inhibiting adenylyl cyclase leading to the intracellular increase or decrease of the secondary messenger cyclic AMP.
The Gβγ subunit plays a variety of roles in cell signalling processes and as such researchers are now examining its potential as a therapeutic drug target for the treatment of many medical conditions.
However, in heart failure there are sustained and elevated levels of catecholamines which result in chronic desensitization of the βAR receptor.
[25] The over expression of GRK2ct has been shown to significantly rescue cardiac function in murine models of heart failure by blocking Gβγ subunit signalling.
