Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Functional Role of a C-Terminal Gβγ-Binding Domain of Cav2.2 Channels

Bin Li, Huijun Zhong, Todd Scheuer and William A. Catterall
Molecular Pharmacology September 2004, 66 (3) 761-769;
Bin Li
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Huijun Zhong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Todd Scheuer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William A. Catterall
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Presynaptic Ca2+ channels are inhibited by neurotransmitters acting through G protein-coupled receptors via a membrane-delimited pathway. Inhibition is reversed by strong depolarization, resulting in prepulse facilitation. Activated G protein βγ subunits (Gβγ) are required for maximal prepulse facilitation. Gβγ binds to multiple sites on Cav2.1, Cav2.2, and Cav2.3 α1 subunits. Here we examine the functional relevance of a C-terminal binding site for Gβγ on Cav2.2b channels, which mediate N-type Ca2+ currents. In vitro binding studies showed that Gβγ subunits bind to the intracellular loop connecting domains I and II and the C-terminal domain of Cav2.2b but not the intracellular loops connecting domains II and III or III and IV. Deletion analysis revealed that the binding site is located near the C terminus, within amino acid residues 2257 to 2336. Directed yeast two-hybrid analysis confirmed this specific binding interaction in vivo in yeast cells. Cav2.2b channels with this site deleted had normal function properties, and they were inhibited essentially normally by strong activation of G proteins with guanosine 5′-3-O-(thio)triphosphate (GTPγS) and were facilitated nearly normally by depolarizing prepulses. Similarly deletion of this site had small, statistically insignificant effects on inhibition of Ca2+ current and on prepulse facilitation in the presence of somatostatin to stimulate receptor-mediated activation of G proteins. In contrast, deletion of the C-terminal Gβγ site substantially reduced the low level of intrinsic prepulse facilitation present at the basal level of G protein activation in tsA-201 cells. Thus, this C-terminal Gβγ binding site contributes to the affinity or efficacy of Gβγ regulation at basal levels of G protein activation. The simplest interpretation of our results is that the C-terminal binding site increases the affinity of Gβγ for the channel but is not required for Gβγ action. C-terminal binding of Gβγ may influence the physiological responsiveness of Ca2+ channels to low-level G protein activation.

  • Received February 26, 2004.
  • Accepted June 10, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

Log in using your username and password

Forgot your user name or password?

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

PreviousNext
Back to top

In this issue

Molecular Pharmacology: 66 (3)
Molecular Pharmacology
Vol. 66, Issue 3
1 Sep 2004
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Functional Role of a C-Terminal Gβγ-Binding Domain of Cav2.2 Channels
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
Citation Tools
Research ArticleArticle

Functional Role of a C-Terminal Gβγ-Binding Domain of Cav2.2 Channels

Bin Li, Huijun Zhong, Todd Scheuer and William A. Catterall
Molecular Pharmacology September 1, 2004, 66 (3) 761-769;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Functional Role of a C-Terminal Gβγ-Binding Domain of Cav2.2 Channels

Bin Li, Huijun Zhong, Todd Scheuer and William A. Catterall
Molecular Pharmacology September 1, 2004, 66 (3) 761-769;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Coordinated Transcriptional Regulation of Cytochrome P450 3As by Nuclear Transcription Factor Y (NF-Y) and Specificity Protein 1 (Sp1)
  • Protocol-dependent differences in IC50 values measured in hERG assays occur in a predictable way and can be used to quantify state preference of drug binding.
  • Statins perturb Gβγ signaling and cell behaviors in a Gγ subtype dependent manner
Show more Article

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2019 by the American Society for Pharmacology and Experimental Therapeutics