Gβ association and effector interaction selectivities of the divergent Gγ subunit Gγ13

Ggamma(13) is a divergent member of the Ggamma subunit family considered to be a component of the gustducin G-protein heterotrimer involved in bitter and sweet taste reception in taste bud cells. Ggamma(13) contains a C-terminal asparagine-proline-tryptophan (NPW) tripeptide, a hallmark of RGS protein Ggamma-like (GGL) domains which dimerize exclusively with Gbeta(5) subunits. In this study, we investigated the functional range of Ggamma(13) assembly with Gbeta subunits using multiple assays of Gbeta association and Gbetagamma effector modulation. Ggamma(13) was observed to associate with all five Gbeta subunits (Gbeta(1-5)) upon co-translation in vitro, as well as function with all five Gbeta subunits in the modulation of Kir3.1/3.4 (GIRK1/4) potassium and N-type (alpha(1B)) calcium channels. Multiple Gbeta/Ggamma(13) pairings were also functional in cellular assays of phospholipase C (PLC) 132 activation and inhibition of Galpha(q)-stimulated PLCbeta1 activity. However, upon cellular co-expression of Ggamma(13) with different Gbeta subunits, only Gbeta(1)/Ggamma(13), Gbeta(3)/Ggamma(13), and Gbeta(4)/Ggamma(13) pairings were found to form stable dimers detectable by co-immunoprecipitation under high-detergent cell lysis conditions. Collectively, these data indicate that Ggamma(13) forms functional Gbetagamma dimers with a range of Gbeta subunits. Coupled with our detection of Ggamma(13) mRNA in mouse and human brain and retina, these results imply that this divergent Ggamma subunit can act in signal transduction pathways other than that dedicated to taste reception in sensory lingual tissue.