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

Dynamin 2 Regulates Riboflavin Endocytosis in Human Placental Trophoblasts

Amy B. Foraker, Abhijit Ray, Tatiana Claro Da Silva, Lisa M. Bareford, Kathleen M. Hillgren, Thomas D. Schmittgen and Peter W. Swaan
Molecular Pharmacology September 2007, 72 (3) 553-562; DOI: https://doi.org/10.1124/mol.107.037101
Amy B. Foraker
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Abhijit Ray
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tatiana Claro Da Silva
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lisa M. Bareford
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathleen M. Hillgren
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas D. Schmittgen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter W. Swaan
  • 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

Riboflavin is thoroughly established to be indispensable in a multitude of cellular oxidation-reduction reactions through its conversion to coenzyme forms flavin mononucleotide and flavin adenine dinucleotide. Despite its physiological importance, little is known about specific mechanisms or proteins involved in regulating its cellular entry in humans. Studies involving biochemical modulators and immunological inhibition assays have indirectly revealed that riboflavin internalization and trafficking occurs at least in part through a clathrin-dependent receptor-mediated endocytic process. Here, using a two-tiered strategy involving RNA interference and the overexpression of dominant-negative constructs, we directly show the involvement of this endocytic mechanism through the requirement of the pluripotent endocytic vesicle scission enzyme, dynamin 2 GTPase, in human placental trophoblasts. Similar to the endocytic control ligand, transferrin, riboflavin is shown to exhibit 50% dependence on the functional expression of dynamin 2 for its active cellular entry. Furthermore, this reduced vitamin uptake correlates with >2-fold higher riboflavin association at the cell surface. In addition, fluorescent ligand endocytosis assays showing colocalization between rhodamine-riboflavin and the immunostained caveolar coat protein, caveolin 1, suggest that the active absorption of this important nutrient involves multiple and distinct endocytosis pathways.

Footnotes

  • This work was supported, in part, by the National Institutes of Health under grant DK56631 (to P.W.S.), a postdoctoral fellowship grant from the Susan G. Komen Foundation (to P.W.S.), and by a predoctoral fellowship sponsored by Eli Lilly and Company (to A.B.F.).

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

  • doi:10.1124/mol.107.037101.

  • ABBREVIATIONS: RME, receptor-mediated endocytosis; B2, riboflavin; CME, clathrin-mediated endocytosis; RNAi, RNA interference; TGF-β, tumor growth factor β; DNM2, dynamin 2 GTPase; CvME, caveolae-mediated endocytosis; siRNA, short-interfering RNA; DLP1, dynamin-like protein 1; TF, transferrin; CAV1, caveolin 1; CTX, cholera toxin subunit B; PC, Pearson's correlation; N, nontargeting; ANOVA, analysis of variance; PBS, phosphate-buffered saline; 3D, three-dimensional;. Rd-RF, rhodamine-riboflavin; DNM2WT, wild-type dynamin 2; DNM2K44A, dominant-negative dynamin 2.

    • Received April 13, 2007.
    • Accepted June 12, 2007.
  • 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: 72 (3)
Molecular Pharmacology
Vol. 72, Issue 3
1 Sep 2007
  • 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.
Dynamin 2 Regulates Riboflavin Endocytosis in Human Placental Trophoblasts
(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

Dynamin 2 Regulates Riboflavin Endocytosis in Human Placental Trophoblasts

Amy B. Foraker, Abhijit Ray, Tatiana Claro Da Silva, Lisa M. Bareford, Kathleen M. Hillgren, Thomas D. Schmittgen and Peter W. Swaan
Molecular Pharmacology September 1, 2007, 72 (3) 553-562; DOI: https://doi.org/10.1124/mol.107.037101

Citation Manager Formats

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

Share
Research ArticleArticle

Dynamin 2 Regulates Riboflavin Endocytosis in Human Placental Trophoblasts

Amy B. Foraker, Abhijit Ray, Tatiana Claro Da Silva, Lisa M. Bareford, Kathleen M. Hillgren, Thomas D. Schmittgen and Peter W. Swaan
Molecular Pharmacology September 1, 2007, 72 (3) 553-562; DOI: https://doi.org/10.1124/mol.107.037101
Reddit logo Twitter logo Facebook 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

  • Analgesic Effects and Mechanisms of Licochalcones
  • Induced Fit Ligand Binding to CYP3A4
  • Englerin A Inhibits T-Type Channels
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