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

Regulation of Renal Outer Medullary Potassium Channel and Renal K+ Excretion by Klotho

Seung-Kuy Cha, Ming-Chang Hu, Hiroshi Kurosu, Makoto Kuro-o, Orson Moe and Chou-Long Huang
Molecular Pharmacology July 2009, 76 (1) 38-46; DOI: https://doi.org/10.1124/mol.109.055780
Seung-Kuy Cha
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ming-Chang Hu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroshi Kurosu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Makoto Kuro-o
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Orson Moe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chou-Long Huang
  • 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

Klotho is an aging-suppression protein predominantly expressed in kidney, parathyroid glands, and choroids plexus of the brain. The extracellular domain of Klotho, a type-1 membrane protein, is secreted into urine and blood and may function as an endocrine or paracrine hormone. The functional role of Klotho in the kidney remains largely unknown. Recent studies reported that treatment by the extracellular domain of Klotho (KLe) increases cell-surface abundance of transient receptor potential vanilloid type isoform 5, an epithelial Ca2+ channel critical for Ca2+ reabsorption in the kidney. Whether Klotho regulates surface expression of other channels in the kidney is not known. Here, we report that KLe treatment increases the cell-membrane abundance of the renal K+ channel renal outer medullary potassium channel 1 (ROMK1) by removing terminal sialic acids from N-glycan of the channel. Removal of sialic acids exposes underlying disaccharide galactose-N-acetylglucosamine, a ligand for a ubiquitous galactoside-binding lectin galectin-1. Binding to galectin-1 at the extracellular surface prevents clathrin-mediated endocytosis of ROMK1 and leads to accumulation of functional channel on the plasma membrane. Intravenous administration of KLe increases the level of Klotho in urine and increases urinary excretion of K+. These results suggest that Klotho may have a broader function in the regulation of ion transport in the kidney.

Footnotes

  • This work was supported by grants from the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grants DK20543, DK59530, DK79328]; the National Institutes of Health National Institute on Aging [Grants AG19712, AG19712]; the American Heart Association [Grant 0440019N]; the Eisai Research Fund; the Ellison Medical Foundation; and the Ted Nash Long Life Foundation. The Consortium for Functional Glycomics was supported by the National Institutes of Health National Institute on Aging [Grant GM62116].

  • ABBREVIATIONS: FGF, fibroblast growth factor; KLe, extracellular domain of Klotho; KL1 and KL2, repeat 1 and 2 of the extracellular domain of Klotho; ROMK1, renal outer medullary potassium channel 1; TRPV5, transient receptor potential vanilloid type isoform 5; HEK, human embryonic kidney; CHO, Chinese hamster ovary; GFP, green fluorescent protein; ST6, α2,6-sialyltransferases; ST6Gal-1, galactosyl-α2,6-sialyltransferase isoform-1; ST3Gal-1, galactosyl-α2,3-sialyltransferase isoform-1; CHC, clathrin heavy chain; Cav-1, caveolin-1; DANA, 2-deoxy-2,3-dehyro-N-acetylneuraminic acid; GnT-V, N-acetylglucosaminyltransferase V; LacNAc, N-acetyllactosamine; GlcNAc, N-acetylglucosamine; SNA, Sambucus nigra agglutinin; siRNA, small interference RNA; PBS, phosphate-buffered saline; DN, dominant-negative; DN DII, dominant-negative dynamin II; WT DII, wild-type dynamin II.

    • Accepted April 6, 2009.
    • Received February 20, 2009.
  • 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: 76 (1)
Molecular Pharmacology
Vol. 76, Issue 1
1 Jul 2009
  • 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.
Regulation of Renal Outer Medullary Potassium Channel and Renal K+ Excretion by Klotho
(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

Regulation of Renal Outer Medullary Potassium Channel and Renal K+ Excretion by Klotho

Seung-Kuy Cha, Ming-Chang Hu, Hiroshi Kurosu, Makoto Kuro-o, Orson Moe and Chou-Long Huang
Molecular Pharmacology July 1, 2009, 76 (1) 38-46; DOI: https://doi.org/10.1124/mol.109.055780

Citation Manager Formats

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

Share
Research ArticleArticle

Regulation of Renal Outer Medullary Potassium Channel and Renal K+ Excretion by Klotho

Seung-Kuy Cha, Ming-Chang Hu, Hiroshi Kurosu, Makoto Kuro-o, Orson Moe and Chou-Long Huang
Molecular Pharmacology July 1, 2009, 76 (1) 38-46; DOI: https://doi.org/10.1124/mol.109.055780
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