Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • 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
  • My Cart

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
  • My Cart
Molecular Pharmacology

Advanced Search

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

Gβγ Binds to the Extreme C Terminus of SNAP25 to Mediate the Action of Gi/o-Coupled G Protein–Coupled Receptors

Zack Zurawski, Shelagh Rodriguez, Karren Hyde, Simon Alford and Heidi E. Hamm
Molecular Pharmacology January 2016, 89 (1) 75-83; DOI: https://doi.org/10.1124/mol.115.101600
Zack Zurawski
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee (Z.Z., K.H., H.E.H.); and Department of Biological Sciences, University of Illinois, Chicago, Illinois (S.R., S.A.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shelagh Rodriguez
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee (Z.Z., K.H., H.E.H.); and Department of Biological Sciences, University of Illinois, Chicago, Illinois (S.R., S.A.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karren Hyde
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee (Z.Z., K.H., H.E.H.); and Department of Biological Sciences, University of Illinois, Chicago, Illinois (S.R., S.A.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon Alford
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee (Z.Z., K.H., H.E.H.); and Department of Biological Sciences, University of Illinois, Chicago, Illinois (S.R., S.A.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heidi E. Hamm
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee (Z.Z., K.H., H.E.H.); and Department of Biological Sciences, University of Illinois, Chicago, Illinois (S.R., S.A.)
  • 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

Gi/o-coupled G protein–coupled receptors can exert an inhibitory effect on vesicle release through several G protein–driven mechanisms, more than one of which may be concurrently present in individual presynaptic terminals. The synaptosomal-associated protein of 25 kDa (SNAP25) is a key downstream effector of Gβγ subunits. It has previously been shown that proteolytic cleavage of SNAP25 by botulinum toxin A reduces the ability of Gβγ to compete with the calcium sensor synaptotagmin 1 (Syt1) for binding to SNAP25 in a calcium-dependent manner. These truncated SNAP25 proteins sustain a low level of exocytosis but are unable to support serotonin-mediated inhibition of exocytosis in lamprey spinal neurons. Here, we generate a SNAP25 extreme C-terminal mutant that is deficient in its ability to bind Gβγ while retaining normal calcium-dependent Syt1 binding to soluble N-ethylmaleimide attachment protein receptor (SNARE) and vesicle release. The SNAP25Δ3 mutant, in which residue G204 is replaced by a stop codon, features a partial reduction in Gβ1γ2 binding in vitro as well as a partial reduction in the ability of the lamprey 5-hydroxytryptamine1b–type serotonin receptor to reduce excitatory postsynaptic current amplitudes, an effect previously shown to be mediated through the interaction of Gβγ with SNAP25. Syt1 calcium-dependent binding to SNAP25Δ3 was reduced by a small extent compared with the wild type. We conclude that the extreme C terminus of SNAP25 is a critical region for the Gβγ-SNARE interaction.

Footnotes

    • Received September 1, 2015.
    • Accepted October 30, 2015.
  • This work was supported by the National Institutes of Health National Eye Institute [R01- EY010291]; and the National Institutes of Health National Institute of Mental Health [MH101679- 01A1]. ZZ was supported by the T32 Training in Pharmacological Sciences, T32 GM07628.

  • All authors declare that no conflicts of interest exist for them within the contents of this article.

  • dx.doi.org/10.1124/mol.115.101600.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 89 (1)
Molecular Pharmacology
Vol. 89, Issue 1
1 Jan 2016
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
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.
Gβγ Binds to the Extreme C Terminus of SNAP25 to Mediate the Action of Gi/o-Coupled G Protein–Coupled Receptors
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

SNAP25 C-terminal Mutants Resistant to Gβγ Inhibition

Zack Zurawski, Shelagh Rodriguez, Karren Hyde, Simon Alford and Heidi E. Hamm
Molecular Pharmacology January 1, 2016, 89 (1) 75-83; DOI: https://doi.org/10.1124/mol.115.101600

Citation Manager Formats

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

Share
Research ArticleArticle

SNAP25 C-terminal Mutants Resistant to Gβγ Inhibition

Zack Zurawski, Shelagh Rodriguez, Karren Hyde, Simon Alford and Heidi E. Hamm
Molecular Pharmacology January 1, 2016, 89 (1) 75-83; DOI: https://doi.org/10.1124/mol.115.101600
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • Fatty Acid Amide Hydrolase in Cisplatin Nephrotoxicity
  • Use-Dependent Relief of A-887826 Inhibition
  • Benzbromarone Relaxes Airway Smooth Muscle via BK Activation
Show more Articles

Similar Articles

Advertisement
  • 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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics