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

Publication ,  Journal Article
Clancy, SM; Fowler, CE; Finley, M; Suen, KF; Arrabit, C; Berton, F; Kosaza, T; Casey, PJ; Slesinger, PA
Published in: Mol Cell Neurosci
February 2005

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.

Duke Scholars

Published In

Mol Cell Neurosci

DOI

ISSN

1044-7431

Publication Date

February 2005

Volume

28

Issue

2

Start / End Page

375 / 389

Location

United States

Related Subject Headings

  • Xenopus
  • Signal Transduction
  • Receptors, G-Protein-Coupled
  • Rats
  • Protein Structure, Tertiary
  • Protein Binding
  • Potassium Channels, Inwardly Rectifying
  • Pertussis Toxin
  • Oocytes
  • Neurons
 

Citation

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Clancy, S. M., Fowler, C. E., Finley, M., Suen, K. F., Arrabit, C., Berton, F., … Slesinger, P. A. (2005). Pertussis-toxin-sensitive Galpha subunits selectively bind to C-terminal domain of neuronal GIRK channels: evidence for a heterotrimeric G-protein-channel complex. Mol Cell Neurosci, 28(2), 375–389. https://doi.org/10.1016/j.mcn.2004.10.009
Clancy, Sinead M., Catherine E. Fowler, Melissa Finley, Ka Fai Suen, Christine Arrabit, Frédérique Berton, Tohru Kosaza, Patrick J. Casey, and Paul A. Slesinger. “Pertussis-toxin-sensitive Galpha subunits selectively bind to C-terminal domain of neuronal GIRK channels: evidence for a heterotrimeric G-protein-channel complex.Mol Cell Neurosci 28, no. 2 (February 2005): 375–89. https://doi.org/10.1016/j.mcn.2004.10.009.
Clancy SM, Fowler CE, Finley M, Suen KF, Arrabit C, Berton F, et al. Pertussis-toxin-sensitive Galpha subunits selectively bind to C-terminal domain of neuronal GIRK channels: evidence for a heterotrimeric G-protein-channel complex. Mol Cell Neurosci. 2005 Feb;28(2):375–89.
Clancy, Sinead M., et al. “Pertussis-toxin-sensitive Galpha subunits selectively bind to C-terminal domain of neuronal GIRK channels: evidence for a heterotrimeric G-protein-channel complex.Mol Cell Neurosci, vol. 28, no. 2, Feb. 2005, pp. 375–89. Pubmed, doi:10.1016/j.mcn.2004.10.009.
Clancy SM, Fowler CE, Finley M, Suen KF, Arrabit C, Berton F, Kosaza T, Casey PJ, Slesinger PA. Pertussis-toxin-sensitive Galpha subunits selectively bind to C-terminal domain of neuronal GIRK channels: evidence for a heterotrimeric G-protein-channel complex. Mol Cell Neurosci. 2005 Feb;28(2):375–389.

Published In

Mol Cell Neurosci

DOI

ISSN

1044-7431

Publication Date

February 2005

Volume

28

Issue

2

Start / End Page

375 / 389

Location

United States

Related Subject Headings

  • Xenopus
  • Signal Transduction
  • Receptors, G-Protein-Coupled
  • Rats
  • Protein Structure, Tertiary
  • Protein Binding
  • Potassium Channels, Inwardly Rectifying
  • Pertussis Toxin
  • Oocytes
  • Neurons