416864.fig.003
Figure 3: Functional crosstalk between G-protein coupled receptors (GPCRs) (which are present in the serotonin, dopamine, acetylcholine system) and GABAA receptors is facilitated through multiple protein kinases and scaffold proteins. GABAA receptor β and γ2 subunits are phosphorylated (P) by PKA and PKC upon the activation of individual GPCRs for dopamine and serotonin. PKA phosphorylation of GABAA receptor β1 and β3 subunits is dependent upon AKAP150/79, which directly interacts with these receptor subunits. AKAP150/79 also binds inactive PKA composed of regulatory (R) and catalytic (C) subunits. In addition, PKC phosphorylates the receptor β1–3 and γ2 subunits. Upon the activation of the appropriate GPCR, PKC-mediated phosphorylation is facilitated by the direct (but independent) interaction of the receptor for activated C kinase (RACK-1) and the β isoform of PKC with the GABAA receptor β1–3 subunits. RACK-1 facilitates functional regulation of GABAA receptors by controlling the activity of PKC associated with these proteins. The GABAA receptor γ2 subunit is also phosphorylated by Src, and this kinase is capable of binding to receptor β and γ2 subunits. Finally, the functional effects of phosphorylation are diverse and range from inhibitions to enhancements of GABAA receptor activity, dependent upon the receptor subunit composition. Reprinted by permission from Elsevier, reprinted from [95].