Gβ Association and Effector Interaction Selectivities of the Divergent Gγ Subunit Gγ13

Bonita L. Blake, Michele R. Wing, Janice Y. Zhou, Qiubo Lei, Jennie R. Hillmann, Cynthia I. Behe, Rebecca A. Morris, T. Kendall Harden, Douglas A. Bayliss, Richard J. Miller, David P. Siderovski*

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

13 is a divergent member of the Gγ subunit family considered to be a component of the gustducin G-protein heterotrimer involved in bitter and sweet taste reception in taste bud cells. Gγ13 contains a C-terminal asparagine-proline-tryptophan (NPW) tripeptide, a hallmark of RGS protein Gγ-like (GGL) domains which dimerize exclusively with Gβ5 subunits. In this study, we investigated the functional range of Gγ13 assembly with Gβ subunits using multiple assays of Gβ association and Gβγ effector modulation. Gγ13 was observed to associate with all five Gβ subunits (Gβ1-5) upon co-translation in vitro, as well as function with all five Gβ subunits in the modulation of Kir3.1/3.4 (GIRK1/4) potassium and N-type (α1B) calcium channels. Multiple Gβ/ Gγ13 pairings were also functional in cellular assays of phospholipase C (PLC) β2 activation and inhibition of Gα q-stimulated PLCβ1 activity. However, upon cellular co-expression of Gγ13 with different Gβ subunits, only Gβ1/Gγ13, Gβ3/Gγ 13, and Gβ4/Gγ13 pairings were found to form stable dimers detectable by co-immunoprecipitation under high-detergent cell lysis conditions. Collectively, these data indicate that Gγ13 forms functional Gβγ dimers with a range of Gβ subunits. Coupled with our detection of Gγ13 mRNA in mouse and human brain and retina, these results imply that this divergent Gγ subunit can act in signal transduction pathways other than that dedicated to taste reception in sensory lingual tissue.

Original languageEnglish (US)
Pages (from-to)49267-49274
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number52
DOIs
StatePublished - Dec 28 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Blake, B. L., Wing, M. R., Zhou, J. Y., Lei, Q., Hillmann, J. R., Behe, C. I., Morris, R. A., Harden, T. K., Bayliss, D. A., Miller, R. J., & Siderovski, D. P. (2001). Gβ Association and Effector Interaction Selectivities of the Divergent Gγ Subunit Gγ13. Journal of Biological Chemistry, 276(52), 49267-49274. https://doi.org/10.1074/jbc.M106565200