ArticleProceedings of the National Academy of Sciences of the United States of America2008
Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 215 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
215 citing papers in PubMed, 3 syntheses or guidelines pooled it, 412 citations in OpenAlex.
- Influence of Klotho Protein Levels in Obesity and Sarcopenia: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Correlation between soluble klotho and chronic kidney disease-mineral and bone disorder in chronic kidney disease: a meta-analysis.Scientific reports · 2024Pooled it
- Correlation between SolubleBioMed research international · 2018Pooled it
- Klotho Deficiency Impairs Distal Potassium Homeostasis Through mTORC1-Dependent Suppression of ROMK.Acta physiologica (Oxford, England) · 2026Article
- Klotho in the kidney distal convolution regulates urinary Klotho excretion and kidney calcium reabsorption, but not phosphate homeostasis.Kidney international · 2026Article
- Glycosylation as a dynamic regulator of RLR and cGAS-STING innate immune signalling pathways.Communications biology · 2026Review
- Associations Between Klotho/FGF-Related Protein Expression in Peripheral Blood Mononuclear Cells, Inflammation, and Muscle Function in Middle-Aged Adults with Obesity: A Pilot Study.International journal of molecular sciences · 2026Article
- Klotho in aging and diseases: molecular features, expressions, and functional implications.Molecular and cellular biochemistry · 2026Review
- Sex-Related Expression of Klotho in Rat Kidneys: Species Differences Between Rats and Mice.International journal of molecular sciences · 2026Article
- The Anti-Inflammatory Actions of Soluble Klotho in Brain Aging and Its Main Associated Diseases.International journal of molecular sciences · 2025Review
- Associations between klotho levels and mortality risk among middle-aged and older adults taking prescription opioids.Preventive medicine reports · 2025Article
- Partial renal deletion of Klotho is not sufficient to impact renal electrolyte handling in distal convoluted tubule specific knock-out mice.Physiological reports · 2025Article
- Conformational landscape of soluble α-klotho revealed by cryogenic electron microscopy.Scientific reports · 2025Article
- Article
- The aging heart: exploring the role of Klotho in cardiac health/function.The journal of cardiovascular aging · 2024Article
- Overexpression of α-Klotho isoforms promotes distinct Effects on BDNF-Induced Alterations in Dendritic Morphology.Molecular neurobiology · 2024Article
- Bioactive Properties of Venoms Isolated from Whiptail Stingrays and the Search for Molecular Mechanisms and Targets.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Conformational landscape of soluble α-klotho revealed by cryogenic electron microscopy.bioRxiv : the preprint server for biology · 2024Article
- Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease-Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows.International journal of molecular sciences · 2024Review
- The ion channel TRPV5 regulates B-cell signaling and activation.Frontiers in immunology · 2024Article
155 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Klotho is a mammalian senescence-suppression protein that has homology with glycosidases. The extracellular domain of Klotho is secreted into urine and blood and may function as a humoral factor. Klotho-deficient mice have accelerated aging and imbalance of ion homeostasis. Klotho treatment increases cell-surface abundance of the renal epithelial Ca(2+) channel TRPV5 by modifying its N-linked glycans. However, the precise sugar substrate and mechanism for regulation by Klotho is not known. Here, we report that the extracellular domain of Klotho activates plasma-membrane resident TRPV5 through removing terminal sialic acids from their glycan chains. Removal of sialic acids exposes underlying disaccharide galactose-N-acetylglucosamine, a ligand for a ubiquitous galactoside-binding lectin galectin-1. Binding to galectin-1 lattice at the extracellular surface leads to accumulation of functional TRPV5 on the plasma membrane. Knockdown of beta-galactoside alpha2,6-sialyltransferase (ST6Gal-1) by RNA interference, but not other sialyltransferases, in a human cell line prevents the regulation by Klotho. Moreover, the regulation by Klotho is absent in a hamster cell line that lacks endogenous ST6Gal-1, but is restored by forced expression of recombinant ST6Gal-1. Thus, Klotho participates in specific removal of alpha2,6-linked sialic acids and regulates cell surface retention of TRPV5 through this activity. This action of Klotho represents a novel mechanism for regulation of the activity of cell-surface glycoproteins and likely contributes to maintenance of calcium balance by Klotho.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.