ArticleProceedings of the National Academy of Sciences of the United States of America2017
Soluble klotho binds monosialoganglioside to regulate membrane microdomains and growth factor signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 90 citations in OpenAlex.
- The Binding of Fibroblast Growth Factor 23 (FGF23) to FGF Receptor-αKlotho Complex Increases Sinoatrial Electrical Activity.Acta physiologica (Oxford, England) · 2026Article
- [Effect of pioglitazone on periodontitis-related renal injury in mice and its relationship with Klotho].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2026Article
- Klotho in aging and diseases: molecular features, expressions, and functional implications.Molecular and cellular biochemistry · 2026Review
- Review
- Klotho's Impact on Cardiovascular Disease, Fractures, and Mortality in Hemodialysis.Kidney international reports · 2025Article
- The Anti-Inflammatory Actions of Soluble Klotho in Brain Aging and Its Main Associated Diseases.International journal of molecular sciences · 2025Review
- Klotho protein: a multifaceted regulator in aging and cancer dynamics.Molecular biology reports · 2025Review
- Identification of metabolism-related subtypes and feature genes of pre-eclampsia.Scientific reports · 2025Article
- Conformational landscape of soluble α-klotho revealed by cryogenic electron microscopy.Scientific reports · 2025Article
- Overexpression of α-Klotho isoforms promotes distinct Effects on BDNF-Induced Alterations in Dendritic Morphology.Molecular neurobiology · 2024Article
- Klotho enhances diastolic function in aged hearts through Sirt1-mediated pathways.GeroScience · 2024Article
- Association ofJournal of diabetes and metabolic disorders · 2024Article
- Conformational landscape of soluble α-klotho revealed by cryogenic electron microscopy.bioRxiv : the preprint server for biology · 2024Article
- Phosphate in Cardiovascular Disease: From New Insights Into Molecular Mechanisms to Clinical Implications.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- 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
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
- Life-Limiting Peripheral Organ Dysfunction in Feline Sandhoff Disease Emerges after Effective CNS Gene Therapy.Annals of neurology · 2023Article
- New concepts in regulation and function of the FGF23.Clinical and experimental medicine · 2023Review
- Klotho: A new therapeutic target in diabetic retinopathy?World journal of diabetes · 2023Review
- TheIndian journal of clinical biochemistry : IJCB · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Soluble klotho, the shed ectodomain of the antiaging membrane protein α-klotho, is a pleiotropic endocrine/paracrine factor with no known receptors and poorly understood mechanism of action. Soluble klotho down-regulates growth factor-driven PI3K signaling, contributing to extension of lifespan, cardioprotection, and tumor inhibition. Here we show that soluble klotho binds membrane lipid rafts. Klotho binding to rafts alters lipid organization, decreases membrane's propensity to form large ordered domains for endocytosis, and down-regulates raft-dependent PI3K/Akt signaling. We identify α2-3-sialyllactose present in the glycan of monosialogangliosides as targets of soluble klotho. α2-3-Sialyllactose is a common motif of glycans. To explain why klotho preferentially targets lipid rafts we show that clustering of gangliosides in lipid rafts is important. In vivo, raft-dependent PI3K signaling is up-regulated in klotho-deficient mouse hearts vs. wild-type hearts. Our results identify ganglioside-enriched lipid rafts to be receptors that mediate soluble klotho regulation of PI3K signaling. Targeting sialic acids may be a general mechanism for pleiotropic actions of soluble klotho.
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Registered trials
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.