ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019
Soluble klotho regulates TRPC6 calcium signaling
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- α-Klotho as a central integrative signalling hub in cognitive function and neuroprotection in neurodegenerative diseases.Metabolic brain disease · 2026Review
- The Anti-Inflammatory Actions of Soluble Klotho in Brain Aging and Its Main Associated Diseases.International journal of molecular sciences · 2025Review
- Overexpression of α-Klotho isoforms promotes distinct Effects on BDNF-Induced Alterations in Dendritic Morphology.Molecular neurobiology · 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
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
- The fibroblast growth factor-Klotho axis at molecular level.Open life sciences · 2023Review
- The controversy of klotho as a potential biomarker in chronic kidney disease.Frontiers in pharmacology · 2022Review
- The Importance of Phosphate Control in Chronic Kidney Disease.Nutrients · 2021Review
- Soluble αKlotho downregulates Orai1-mediated store-operated CaPflugers Archiv : European journal of physiology · 2021Article
- An Overview of FGF-23 as a Novel Candidate Biomarker of Cardiovascular Risk.Frontiers in physiology · 2021Review
- The Protective Role of Klotho in CKD-Associated Cardiovascular Disease.Kidney diseases (Basel, Switzerland) · 2020Review
- A Land of Controversy: Fibroblast Growth Factor-23 and Uremic Cardiac Hypertrophy.Journal of the American Society of Nephrology : JASN · 2020Review
- Klotho rewires cellular metabolism of breast cancer cells through alteration of calcium shuttling and mitochondrial activity.Oncogene · 2020Article
- Soluble Alpha-Klotho Alleviates Cardiac Fibrosis without Altering Cardiomyocytes Renewal.International journal of molecular sciences · 2020Article
- Modulation of Calcium Transients in Cardiomyocytes by Transient Receptor Potential Canonical 6 Channels.Frontiers in physiology · 2020Article
- FGF23 induced left ventricular hypertrophy mediated by FGFR4 signaling in the myocardium is attenuated by soluble Klotho in mice.Journal of molecular and cellular cardiology · 2020Article
- Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications.Frontiers in neuroscience · 2020Review
- αKlotho-FGF23 interactions and their role in kidney disease: a molecular insight.Cellular and molecular life sciences : CMLS · 2019Review
- The Effects of the Anti-aging Protein Klotho on Mucociliary Clearance.Frontiers in medicine · 2019Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Soluble klotho (sKlotho), the shed ectodomain of α-klotho, protects the heart by down-regulating transient receptor potential canonical isoform 6 (TRPC6)-mediated calcium signaling. Binding to α2-3-sialyllactose moiety of gangliosides in lipid rafts and inhibition of raft-dependent signaling underlies the mechanism. A recent 3-Å X-ray structure of sKlotho in complex with fibroblast growth factor receptor (FGFR) and fibroblast growth factor 23 (FGF23) indicates that its β6α6 loop might block access to the proposed binding site for α2-3-sialyllactose. It was concluded that sKlotho only functions in complex with FGFR and FGF23 and that sKlotho's pleiotropic effects all depend on FGF23. Here, we report that sKlotho can inhibit TRPC6 channels expressed in cells lacking endogenous FGFRs. Structural modeling and molecular docking show that a repositioned β6α6 loop allows sKlotho to bind α2-3-sialyllactose. Molecular dynamic simulations further show the α2-3-sialyllactose-bound sKlotho complex to be stable. Domains mimicking sKlotho's sialic acid-recognizing activity inhibit TRPC6. The results strongly support the hypothesis that sKlotho can exert effects independent of FGF23 and FGFR.-Wright, J. D., An, S.-W., Xie, J., Lim, C., Huang, C.-L. Soluble klotho regulates TRPC6 calcium signaling
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