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, Chou Long Huang

Research output: Contribution to journalArticle

132 Citations (Scopus)

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 Ca 2+ 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.

Original languageEnglish
Pages (from-to)38-46
Number of pages9
JournalMolecular pharmacology
Volume76
Issue number1
DOIs
Publication statusPublished - 2009 Jul 1

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Potassium Channels
Kidney
Galectin 1
Sialic Acids
Cell Membrane
Urine
TRPV Cation Channels
Clathrin
Choroid Plexus
Parathyroid Glands
Acetylglucosamine
Disaccharides
Ion Transport
Endocytosis
Renal Elimination
Galactose
Intravenous Administration
Polysaccharides
Protein Isoforms
Membrane Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Cha, Seung Kuy ; Hu, Ming Chang ; Kurosu, Hiroshi ; Kuro-O, Makoto ; Moe, Orson ; Huang, Chou Long. / Regulation of renal outer medullary potassium channel and renal K + excretion by Klotho. In: Molecular pharmacology. 2009 ; Vol. 76, No. 1. pp. 38-46.
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Regulation of renal outer medullary potassium channel and renal K + excretion by Klotho. / Cha, Seung Kuy; Hu, Ming Chang; Kurosu, Hiroshi; Kuro-O, Makoto; Moe, Orson; Huang, Chou Long.

In: Molecular pharmacology, Vol. 76, No. 1, 01.07.2009, p. 38-46.

Research output: Contribution to journalArticle

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