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dc.contributor.author
Dalton, George
dc.contributor.author
An, Sung-Wan
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Al-Juboori, Saif I.
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Nischan, Nicole
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Yoon, Joonho
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Dobrinskikh, Evgenia
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Hilgemann, Donald W.
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Xie, Jian
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Luby-Phelps, Kate
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Kohler, Jennifer J.
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Birnbaumer, Lutz
dc.contributor.author
Huang, Chou-Long
dc.date.available
2018-06-08T15:05:27Z
dc.date.issued
2017-01
dc.identifier.citation
Dalton, George; An, Sung-Wan; Al-Juboori, Saif I.; Nischan, Nicole; Yoon, Joonho; et al.; Soluble klotho binds monosialoganglioside to regulate membrane microdomains and growth factor signaling; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 114; 4; 1-2017; 752-757
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/47856
dc.description.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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Gangliosides
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Lipid Rafts
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Sialic Acids
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Soluble Klotho
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Trpc6
dc.subject.classification
Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Soluble klotho binds monosialoganglioside to regulate membrane microdomains and growth factor signaling
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-06T19:40:59Z
dc.journal.volume
114
dc.journal.number
4
dc.journal.pagination
752-757
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Dalton, George. University of Texas Southwestern Medical Center; Estados Unidos
dc.description.fil
Fil: An, Sung-Wan. University of Texas Southwestern Medical Center; Estados Unidos
dc.description.fil
Fil: Al-Juboori, Saif I.. University of Colorado Denver; Estados Unidos
dc.description.fil
Fil: Nischan, Nicole. University of Texas Southwestern Medical Center; Estados Unidos
dc.description.fil
Fil: Yoon, Joonho. University of Texas Southwestern Medical Center; Estados Unidos
dc.description.fil
Fil: Dobrinskikh, Evgenia. University of Colorado Denver; Estados Unidos
dc.description.fil
Fil: Hilgemann, Donald W.. University of Texas Southwestern Medical Center; Estados Unidos
dc.description.fil
Fil: Xie, Jian. University of Texas Southwestern Medical Center; Estados Unidos
dc.description.fil
Fil: Luby-Phelps, Kate. University of Texas Southwestern Medical Center; Estados Unidos
dc.description.fil
Fil: Kohler, Jennifer J.. University of Texas Southwestern Medical Center; Estados Unidos
dc.description.fil
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences; Estados Unidos. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas; Argentina
dc.description.fil
Fil: Huang, Chou-Long. University of Texas Southwestern Medical Center; Estados Unidos
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1073/pnas.1620301114
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/114/4/752
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