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dc.contributor.authorMüller, Margit Sen
dc.contributor.authorFouyssac, Maximeen
dc.contributor.authorTaylor, Colinen
dc.date.accessioned2018-09-08T06:35:38Z
dc.date.available2018-09-08T06:35:38Z
dc.date.issued2018-11en
dc.identifier.issn0960-9822
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279949
dc.description.abstractAfter its uptake into the cytosol, intracellular glucose is phosphorylated to glucose-6-phosphate (G6P), trapping it within the cell and preparing it for metabolism. In glucose-exporting tissues, like liver, G6P is transported into the ER, where it is dephosphorylated by G6Pase-α. The glucose is then returned to the cytosol for export [1, 2]. Defects in these pathways cause glycogen storage diseases [1]. G6Pase-, an isozyme of G6Pase-α, is widely expressed [3, 4]. Its role in cells that do not export glucose is unclear, although mutations in G6Pase- cause severe and widespread abnormalities [5-7]. Astrocytes, the most abundant cells in the brain, provide metabolic support to neurons, facilitated by astrocytic endfeet that contact blood capillaries or neurons [8-12]. Perivascular endfeet are the main site of glucose uptake by astrocytes [13], but in human brain they may be several millimeters away from the perineuronal processes [14]. We show that cultured human foetal astrocytes express G6Pase-, but not G6Pase-α. ER-targeted glucose sensors [15, 16] reveal that G6Pase- allows the ER of human astrocytes to accumulate glucose by importing G6P from the cytosol. Glucose uptake by astrocytes, ATP production and Ca2+ accumulation by the ER are attenuated after knockdown of G6Pase- using lentivirus-delivered shRNA, and substantially rescued by expression of G6Pase-α. We suggest that G6Pase- activity allows effective uptake of glucose by astrocytes, and we speculate that it allows the ER to function as an intracellular ‘highway’ delivering glucose from perivascular endfeet to the perisynaptic processes.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAstrocytesen
dc.subjectEndoplasmic Reticulumen
dc.subjectFetusen
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectRatsen
dc.subjectRats, Sprague-Dawleyen
dc.subjectGlucose-6-Phosphataseen
dc.subjectGlucoseen
dc.subjectBiological Transporten
dc.subjectMaleen
dc.titleEffective Glucose Uptake by Human Astrocytes Requires Its Sequestration in the Endoplasmic Reticulum by Glucose-6-Phosphatase-β.en
dc.typeArticle
prism.endingPage3486.e4
prism.issueIdentifier21en
prism.publicationDate2018en
prism.publicationNameCurrent biology : CBen
prism.startingPage3481
prism.volume28en
dc.identifier.doi10.17863/CAM.27317
dcterms.dateAccepted2018-08-29en
rioxxterms.versionofrecord10.1016/j.cub.2018.08.060en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-11en
dc.contributor.orcidFouyssac, Maxime [0000-0002-9496-5836]
dc.contributor.orcidTaylor, Colin [0000-0001-7771-1044]
dc.identifier.eissn1879-0445
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (101844/Z/13/Z)
pubs.funder-project-idEuropean Commission (658386)
cam.orpheus.successThu Jan 30 10:54:30 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International