title: Glucose transporter type 10-lacking in arterial tortuosity syndrome-facilitates dehydroascorbic acid transport.
abstract: Loss-of-function mutations in the gene encoding GLUT10 are responsible for arterial tortuosity syndrome (ATS), a rare connective tissue disorder. In this study GLUT10-mediated dehydroascorbic acid (DAA) transport was investigated, supposing its involvement in the pathomechanism. GLUT10 protein produced by in vitro translation and incorporated into liposomes efficiently transported DAA. Silencing of GLUT10 decreased DAA transport in immortalized human fibroblasts whose plasma membrane was selectively permeabilized. Similarly, the transport of DAA through endomembranes was markedly reduced in fibroblasts from ATS patients. Re-expression of GLUT10 in patients' fibroblasts restored DAA transport activity. The present results demonstrate that GLUT10 is a DAA transporter and DAA transport is diminished in the endomembranes of fibroblasts from ATS patients.
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
authors.forename: Csilla E
authors.initials: CE
authors.lastname: Németh
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Marcolongo
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gamberucci
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Fulceri
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Italy.
authors.forename: Angiolo
authors.initials: A
authors.lastname: Benedetti
authors.affiliation: Division of Biology and Genetics, Department of Molecular and Translational Medicine, Medical Faculty, University of Brescia, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Zoppi
authors.affiliation: Division of Biology and Genetics, Department of Molecular and Translational Medicine, Medical Faculty, University of Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ritelli
authors.affiliation: Division of Biology and Genetics, Department of Molecular and Translational Medicine, Medical Faculty, University of Brescia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Chiarelli
authors.affiliation: Division of Biology and Genetics, Department of Molecular and Translational Medicine, Medical Faculty, University of Brescia, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Colombi
authors.affiliation: Center for Medical Genetics, Ghent University, Belgium.
authors.forename: Andy
authors.initials: A
authors.lastname: Willaert
authors.affiliation: Center for Medical Genetics, Ghent University, Belgium.
authors.forename: Bert L
authors.initials: BL
authors.lastname: Callewaert
authors.affiliation: Center for Medical Genetics, Ghent University, Belgium.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Coucke
authors.affiliation: Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
authors.forename: Pál
authors.initials: P
authors.lastname: Gróf
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
authors.forename: Szilvia K
authors.initials: SK
authors.lastname: Nagy
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Mészáros
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Bánhegyi
authors.affiliation: Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Margittai
mesh_terms: D001158:Arteries / Q000002:abnormalities*; D001205:Ascorbic Acid / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003683:Dehydroascorbic Acid / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051246:Glucose Transport Proteins, Facilitative / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D007593:Joint Instability / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D012873:Skin Diseases, Genetic / Q000235:genetics*; D054079:Vascular Malformations / Q000235:genetics*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D034741:RNA, Small Interfering; C430746:SLC2A10 protein, human; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid
keywords: Fe2+/2-oxoglutarate-dependent dehydrogenases; GLUT10; arterial tortuosity syndrome; ascorbate; dehydroascorbic acid; endomembranes