title: G beta association and effector interaction selectivities of the divergent G gamma subunit G gamma(13).
abstract: G gamma(13) is a divergent member of the G gamma subunit family considered to be a component of the gustducin G-protein heterotrimer involved in bitter and sweet taste reception in taste bud cells. G gamma(13) contains a C-terminal asparagine-proline-tryptophan (NPW) tripeptide, a hallmark of RGS protein G gamma-like (GGL) domains which dimerize exclusively with G beta(5) subunits. In this study, we investigated the functional range of G gamma(13) assembly with G beta subunits using multiple assays of G beta association and G beta gamma effector modulation. G gamma(13) was observed to associate with all five G beta subunits (G beta(1-5)) upon co-translation in vitro, as well as function with all five G beta subunits in the modulation of Kir3.1/3.4 (GIRK1/4) potassium and N-type (alpha(1B)) calcium channels. Multiple G beta/G gamma(13) pairings were also functional in cellular assays of phospholipase C (PLC) beta 2 activation and inhibition of G alpha(q)-stimulated PLC beta 1 activity. However, upon cellular co-expression of G gamma(13) with different G beta subunits, only G beta(1)/G gamma(13), G beta(3)/G gamma(13), and G beta(4)/G gamma(13) pairings were found to form stable dimers detectable by co-immunoprecipitation under high-detergent cell lysis conditions. Collectively, these data indicate that G gamma(13) forms functional G beta gamma dimers with a range of G beta subunits. Coupled with our detection of G gamma(13) mRNA in mouse and human brain and retina, these results imply that this divergent G gamma subunit can act in signal transduction pathways other than that dedicated to taste reception in sensory lingual tissue.
authors.affiliation: Department of Pharmacology, University of North Carolina Neuroscience Center, Chapel Hill, North Carolina 27599-7365, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Blake
authors.forename: M R
authors.initials: MR
authors.lastname: Wing
authors.forename: J Y
authors.initials: JY
authors.lastname: Zhou
authors.forename: Q
authors.initials: Q
authors.lastname: Lei
authors.forename: J R
authors.initials: JR
authors.lastname: Hillmann
authors.forename: C I
authors.initials: CI
authors.lastname: Behe
authors.forename: R A
authors.initials: RA
authors.lastname: Morris
authors.forename: T K
authors.initials: TK
authors.lastname: Harden
authors.forename: D A
authors.initials: DA
authors.lastname: Bayliss
authors.forename: R J
authors.initials: RJ
authors.lastname: Miller
authors.forename: D P
authors.initials: DP
authors.lastname: Siderovski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002460:Cell Line; D019281:Dimerization; D004789:Enzyme Activation; D049452:Green Fluorescent Proteins; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D054799:Phospholipase C beta; D015221:Potassium Channels / Q000378:metabolism*; D020033:Protein Isoforms; D021122:Protein Subunits; D016415:Sequence Alignment; D014018:Tissue Distribution; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D020864:Calcium Channels, N-Type; D007202:Indicators and Reagents; D007527:Isoenzymes; D008164:Luminescent Proteins; D015221:Potassium Channels; D020033:Protein Isoforms; D021122:Protein Subunits; D049452:Green Fluorescent Proteins; D010738:Type C Phospholipases; C518033:PLCB1 protein, human; C518036:PLCB2 protein, human; C518039:PLCB3 protein, human; C518042:PLCB4 protein, human; D054799:Phospholipase C beta; C518034:Plcb1 protein, mouse; C518037:Plcb2 protein, mouse; C518040:Plcb3 protein, mouse; C518043:Plcb4 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins