Journal article
Regulation of Renal Outer Medullary Potassium Channel and Renal K+ Excretion by Klotho
Molecular pharmacology, Vol.76(1), pp.38-46
07/01/2009
DOI: 10.1124/mol.109.055780
PMCID: PMC2701452
PMID: 19349416
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.
Details
- Title: Subtitle
- Regulation of Renal Outer Medullary Potassium Channel and Renal K+ Excretion by Klotho
- Creators
- Seung-Kuy Cha - The University of Texas Southwestern Medical CenterMing-Chang Hu - The University of Texas Southwestern Medical CenterHiroshi Kurosu - The University of Texas Southwestern Medical CenterMakoto Kuro-o - The University of Texas Southwestern Medical CenterOrson Moe - The University of Texas Southwestern Medical CenterChou-Long Huang - The University of Texas Southwestern Medical Center
- Resource Type
- Journal article
- Publication Details
- Molecular pharmacology, Vol.76(1), pp.38-46
- DOI
- 10.1124/mol.109.055780
- PMID
- 19349416
- PMCID
- PMC2701452
- NLM abbreviation
- Mol Pharmacol
- ISSN
- 0026-895X
- eISSN
- 1521-0111
- Publisher
- Amer Soc Pharmacology Experimental Therapeutics
- Number of pages
- 9
- Grant note
- DK20543; DK59530; DK79328 / National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01DK059530 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) Ellison Medical Foundation; Lawrence Ellison Foundation Ted Nash Long Life Foundation AG19712; GM62116 / National Institutes of Health National Institute on Aging; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) 0440019N / American Heart Association Eisai Research Fund
- Language
- English
- Date published
- 07/01/2009
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359938902771
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