Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

An N-Terminal Polybasic Motif of Gαq Is Required for Signaling and Influences Membrane Nanodomain Distribution

Marykate Crouthamel, Daniel Abankwa, Li Zhang, Cherisse DiLizio, David R. Manning, John F. Hancock and Philip B. Wedegaertner
Molecular Pharmacology October 2010, 78 (4) 767-777; DOI: https://doi.org/10.1124/mol.110.066340
Marykate Crouthamel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel Abankwa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cherisse DiLizio
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David R. Manning
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John F. Hancock
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philip B. Wedegaertner
  • 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

Regions of basic amino acids in proteins can promote membrane localization through electrostatic interactions with negatively charged membrane lipid head groups. Previous work showed that the heterotrimeric G protein subunit αq contains a polybasic region in its N terminus that contributes to plasma membrane localization. Here, the role of the N-terminal polybasic region of αq in signaling was addressed. For αq mutants, loss of plasma membrane localization correlated with loss of signaling function, as measured by the ability to couple activated G protein-coupled receptors (GPCRs) to stimulation of inositol phosphate production. However, recovery of plasma membrane localization of αq polybasic mutants by introduction of a site for myristoylation or by coexpression of βγ failed to recover signaling, suggesting a role for N-terminal basic amino acids of αq beyond simple plasma membrane localization. It is noteworthy that an αq4Q mutant, containing glutamine substitutions at arginines 27, 30, 31, and 34, was identified that failed to mediate signaling yet retained plasma membrane localization. Although αq4Q failed to couple activated receptors to inositol phosphate production, it was able to bind βγ, bind RGS4 in an activation-dependent manner, stimulate inositol phosphate production in a receptor-independent manner, and productively interact with a GPCR in isolated membranes. It is noteworthy that αq4Q showed a differing localization to plasma membrane nanodomains compared with wild-type αq. Thus, basic amino acids in the N terminus of αq can affect its lateral segregation on plasma membranes, and changes in such lateral segregation may be responsible for the observed signaling defects of αq4Q.

Footnotes

  • This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grants GM56444, GM066717, GM066717]; the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant DK07705]; and the Swiss National Science Foundation Fellowship [Grant PA00A-111446].

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.110.066340.

  • ABBREVIATIONS:

    GPCR
    G protein-coupled receptor
    PM
    plasma membrane
    HEK
    human embryonic kidney
    HA
    hemagglutinin
    PAGE
    polyacrylamide gel electrophoresis
    RGS
    regulator of G protein signaling
    FBS
    fetal bovine serum
    PMSF
    phenylmethylsulfonyl fluoride
    MOI
    multiplicity of infection
    FRET
    fluorescence resonance energy transfer
    PLC-β
    phospholipase Cβ
    mCFP
    monomeric cyan fluorescent protein
    M3R
    M3 receptor
    Sf9
    Spodoptera frugiperda
    α2AR
    α2 adrenergic receptor
    [35S]GTPγS
    guanosine 5′-O-(3-[35S]thio)triphosphate
    UK14304
    5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline
    IP
    inositol phosphate
    U46619
    (5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2 -oxabicyclo[2.2.1]hept-5-yl]-5-heptenoic acid
    NTA
    nitrilotriacetic acid.

  • Received May 12, 2010.
  • Accepted July 21, 2010.
  • Copyright © 2010 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: 78 (4)
Molecular Pharmacology
Vol. 78, Issue 4
1 Oct 2010
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • 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.
An N-Terminal Polybasic Motif of Gαq Is Required for Signaling and Influences Membrane Nanodomain Distribution
(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

An N-Terminal Polybasic Motif of Gαq Is Required for Signaling and Influences Membrane Nanodomain Distribution

Marykate Crouthamel, Daniel Abankwa, Li Zhang, Cherisse DiLizio, David R. Manning, John F. Hancock and Philip B. Wedegaertner
Molecular Pharmacology October 1, 2010, 78 (4) 767-777; DOI: https://doi.org/10.1124/mol.110.066340

Citation Manager Formats

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

An N-Terminal Polybasic Motif of Gαq Is Required for Signaling and Influences Membrane Nanodomain Distribution

Marykate Crouthamel, Daniel Abankwa, Li Zhang, Cherisse DiLizio, David R. Manning, John F. Hancock and Philip B. Wedegaertner
Molecular Pharmacology October 1, 2010, 78 (4) 767-777; DOI: https://doi.org/10.1124/mol.110.066340
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • GABAAR Molecular Identity in Oligodendrocytes
  • Editing TOP2α Intron-19 5′ SS Circumvents Drug Resistance
  • SerpinA3N and drug induced liver injury
Show more Articles

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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics