Please use this identifier to cite or link to this item: https://repositorio.uca.edu.ar/handle/123456789/8734
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dc.contributor.authorDalton, Georgees
dc.contributor.authorAn, Sung-Wanes
dc.contributor.authorAl-Juboori, Saif I.es
dc.contributor.authorNischan, Nicolees
dc.contributor.authorYoon, Joonhoes
dc.contributor.authorDobrinskikh, Evgeniaes
dc.contributor.authorHilgemann, Donald W.es
dc.contributor.authorXie, Jianes
dc.contributor.authorLuby-Phelps, Katees
dc.contributor.authorKohler, Jennifer J.es
dc.contributor.authorBirnbaumer, Lutzes
dc.contributor.authorHuang, Chou-Longes
dc.date.accessioned2019-09-12T20:07:24Z-
dc.date.available2019-09-12T20:07:24Z-
dc.date.issued2017-
dc.identifier.citationDalton G, An S-W, Al-Juboori SI, et al. Soluble klotho binds monosialoganglioside to regulate membrane microdomains and growth factor signaling. Proceedings of the National Academy of Sciences. 2017;114(4):752-757. doi:10.1073/pnas.1620301114 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8734es
dc.identifier.issn0027-8424-
dc.identifier.issn1091-6490 (online)-
dc.identifier.urihttps://repositorio.uca.edu.ar/handle/123456789/8734-
dc.description.abstractAbstract: 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.es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherNational Academy of Scienceses
dc.rightsAcceso Abierto*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.sourceProceedings of the National Academy of Sciences. 2017;114(4):752-757es
dc.subjectTUMORESes
dc.subjectPROTEINASes
dc.subjectMEMBRANAS CELULARESes
dc.subjectLIPIDOSes
dc.titleSoluble klotho binds monosialoganglioside to regulate membrane microdomains and growth factor signalinges
dc.typeArtículoes
dc.identifier.doi10.1073/pnas.1620301114-
dc.identifier.pmid28069944-
uca.disciplinaMEDICINAes
uca.issnrd1es
uca.affiliationFil: Dalton, George. University of Texas Southwestern Medical Center. Department of Medicine; Estados Unidoses
uca.affiliationFil: An, Sung-Wan. University of Texas Southwestern Medical Center. Department of Medicine; Estados Unidoses
uca.affiliationFil: Al-Juboori, Saif I. University of Colorado Denver. Department of Electrical Engineering; Estados Unidoses
uca.affiliationFil: Nischan, Nicole. University of Texas Southwestern Medical Center. Department of Biochemistry; Estados Unidoses
uca.affiliationFil: Yoon, Joonho. University of Texas Southwestern Medical Center. Department of Medicine; Estados Unidoses
uca.affiliationFil: Dobrinskikh, Evgenia. University of Colorado Denver. Department of Medicine; Estados Unidoses
uca.affiliationFil: Hilgemann, Donald W. University of Texas Southwestern Medical Center. Department of Physiology; Estados Unidoses
uca.affiliationFil: Xie, Jian. University of Texas Southwestern Medical Center. Department of Medicine; Estados Unidoses
uca.affiliationFil: Luby-Phelps, Kate. University of Texas Southwestern Medical Center. Department of Cell Biology; Estados Unidoses
uca.affiliationFil: Luby-Phelps, Kate. University of Texas Southwestern Medical Center. Live Cell Imaging Core Facility; Estados Unidoses
uca.affiliationFil: Kohler, Jennifer J. University of Texas Southwestern Medical Center. Department of Biochemistry; Estados Unidoses
uca.affiliationFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentinaes
uca.affiliationFil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Neurobiology Laboratory; Estados Unidoses
uca.affiliationFil: Huang, Chou-Long. University of Texas Southwestern Medical Center. Department of Medicine; Estados Unidoses
uca.versionpublishedVersiones
item.languageiso639-1en-
item.grantfulltextopen-
item.fulltextWith Fulltext-
crisitem.author.deptInstituto de Investigaciones Biomédicas - BIOMED-
crisitem.author.deptLaboratorio de Función y Farmacología de Canales Iónicos-
crisitem.author.deptConsejo Nacional de Investigaciones Científicas y Técnicas-
crisitem.author.orcid0000-0002-0775-8661-
crisitem.author.parentorgFacultad de Ciencias Médicas-
crisitem.author.parentorgInstituto de Investigaciones Biomédicas - BIOMED-
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