Pertussis-toxin-sensitive Galpha subunits selectively bind to C-terminal domain of neuronal GIRK channels: evidence for a heterotrimeric G-protein-channel complex.

Journal Article (Journal Article)

Neuronal G-protein-gated inwardly rectifying potassium (Kir3; GIRK) channels are activated by G-protein-coupled receptors that selectively interact with PTX-sensitive (Galphai/o) G proteins. Although the Gbetagamma dimer is known to activate GIRK channels, the role of the Galphai/o subunit remains unclear. Here, we established that Galphao subunits co-immunoprecipitate with neuronal GIRK channels. In vitro binding studies led to the identification of six amino acids in the GIRK2 C-terminal domain essential for Galphao binding. Further studies suggested that the Galphai/obetagamma heterotrimer binds to the GIRK2 C-terminal domain via Galpha and not Gbetagamma. Galphai/o binding-impaired GIRK2 channels exhibited reduced receptor-activated currents, but retained normal ethanol- and Gbetagamma-activated currents. Finally, PTX-insensitive Galphaq or Galphas subunits did not bind to the GIRK2 C-terminus. Together, these results suggest that the interaction of PTX-sensitive Galphai/o subunit with the GIRK2 C-terminal domain regulates G-protein receptor coupling, and may be important for establishing specific Galphai/o signaling pathways.

Full Text

Duke Authors

Cited Authors

  • Clancy, SM; Fowler, CE; Finley, M; Suen, KF; Arrabit, C; Berton, F; Kosaza, T; Casey, PJ; Slesinger, PA

Published Date

  • February 2005

Published In

Volume / Issue

  • 28 / 2

Start / End Page

  • 375 - 389

PubMed ID

  • 15691717

International Standard Serial Number (ISSN)

  • 1044-7431

Digital Object Identifier (DOI)

  • 10.1016/j.mcn.2004.10.009


  • eng

Conference Location

  • United States