Direct binding of G-protein βγ complex to voltage-dependent calcium channels

M DE WAARD; H LIU; D WALKER; V. E. S SCOTT; C. A GURNETT; K. P CAMPBELL

doi:10.1038/385446a0

Back

Direct binding of G-protein βγ complex to voltage-dependent calcium channels

Journal article

Peer reviewed

Direct binding of G-protein βγ complex to voltage-dependent calcium channels

M DE WAARD, H LIU, D WALKER, V. E. S SCOTT, C. A GURNETT and K. P CAMPBELL

Nature (London), Vol.385(6615), pp.446-450

1997

DOI: 10.1038/385446a0

View Online

Abstract

Voltage-dependent Ca2+ channels play a central role in controlling neurotransmitter release at the synapse1,2. They can be inhibited by certain G-protein-coupled receptors, acting by a pathway intrinsic to the membrane3–6. Here we show that this inhibition results from a direct interaction between the G-protein βλ complex and the pore-forming α1 subunits of several types of these channels7. The interaction is mediated by the cytoplasmic linker connecting the first and second transmembrane repeats. Within this linker, binding occurs both in the α1 interaction domain (AID)8, which also mediates the interaction between the α1 and β subunits of the channel, and in a second downstream sequence. Further analysis of the binding site showed that several amino-terminal residues in the AID are critical for Gβλ binding, defining a site distinct from the carboxy-terminal residues shown to be essential for binding the β-subunit of the Ca2+ channel9. Mutation of an arginine residue within the N-terminal motif abolished βλ binding and rendered the channel refractory to G-protein modulation when expressed in Xenopus oocytes, showing that the interaction is indeed responsible for G-protein-dependent modulation of Ca2+ channel activity.

Fundamental and applied biological sciences. Psychology

Biological and medical sciences

Molecular and cellular biology

Cell structures and functions

Cell membranes. Ionic channels. Membrane pores

Details

Title: Subtitle: Direct binding of G-protein βγ complex to voltage-dependent calcium channels
Creators: M DE WAARD - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Program in Neuroscience, University of Iowa College of Medicine, Iowa City, Iowa 52242, United States
H LIU - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Program in Neuroscience, University of Iowa College of Medicine, Iowa City, Iowa 52242, United States
D WALKER - INSERM U464, Institut Jean Roche, Faculté de Médecine Nord, Boulevard Pierre Dramard, 13916 Marseille, France
V. E. S SCOTT - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Program in Neuroscience, University of Iowa College of Medicine, Iowa City, Iowa 52242, United States
C. A GURNETT - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Program in Neuroscience, University of Iowa College of Medicine, Iowa City, Iowa 52242, United States
K. P CAMPBELL - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Program in Neuroscience, University of Iowa College of Medicine, Iowa City, Iowa 52242, United States
Resource Type: Journal article
Publication Details: Nature (London), Vol.385(6615), pp.446-450
Publisher: Nature Publishing; London
DOI: 10.1038/385446a0
ISSN: 0028-0836
eISSN: 1476-4687
Language: English
Date published: 1997
Academic Unit: Molecular Physiology and Biophysics; Neurology; Iowa Neuroscience Institute
Record Identifier: 9984020869302771

Metrics

6 Record Views

See more details