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Int J Mol Sci. 2017 Aug 22;18(8). pii: E1820. doi: 10.3390/ijms18081820.

GLUT10-Lacking in Arterial Tortuosity Syndrome-Is Localized to the Endoplasmic Reticulum of Human Fibroblasts.

Author information

1
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy. alessandra.gamberucci@unisi.it.
2
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy. paola.marcolongo@unisi.it.
3
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, 1094 Budapest, Hungary. nemeth.csilla@med.semmelweis-univ.hu.
4
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy. nicoletta.zoppi@unibs.it.
5
Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, Budapest University of Technology and Economics, 1111 Budapest, Hungary. szarka@mail.bme.hu.
6
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy. nicola.chiarelli@unibs.it.
7
Department of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, Hungary. tamas@hegelab.org.
8
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy. marco.ritelli@unibs.it.
9
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy. g.carini001@unibs.it.
10
Center for Medical Genetics, Ghent University, B-9000 Ghent, Belgium. Andy.Willaert@UGent.be.
11
Center for Medical Genetics, Ghent University, B-9000 Ghent, Belgium. Bert.Callewaert@UGent.be.
12
Center for Medical Genetics, Ghent University, B-9000 Ghent, Belgium. Paul.Coucke@UGent.be.
13
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy. benedetti@unisi.it.
14
Institute of Clinical Experimental Research, Semmelweis University, 1094 Budapest, Hungary. margittai.eva@med.semmelweis-univ.hu.
15
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy. rosella.fulceri@unisi.it.
16
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, 1094 Budapest, Hungary. banhegyi.gabor@med.semmelweis-univ.hu.
17
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy. marina.colombi@unibs.it.

Abstract

GLUT10 belongs to a family of transporters that catalyze the uptake of sugars/polyols by facilitated diffusion. Loss-of-function mutations in the SLC2A10 gene encoding GLUT10 are responsible for arterial tortuosity syndrome (ATS). Since subcellular distribution of the transporter is dubious, we aimed to clarify the localization of GLUT10. In silico GLUT10 localization prediction suggested its presence in the endoplasmic reticulum (ER). Immunoblotting showed the presence of GLUT10 protein in the microsomal, but not in mitochondrial fractions of human fibroblasts and liver tissue. An even cytosolic distribution with an intense perinuclear decoration of GLUT10 was demonstrated by immunofluorescence in human fibroblasts, whilst mitochondrial markers revealed a fully different decoration pattern. GLUT10 decoration was fully absent in fibroblasts from three ATS patients. Expression of exogenous, tagged GLUT10 in fibroblasts from an ATS patient revealed a strict co-localization with the ER marker protein disulfide isomerase (PDI). The results demonstrate that GLUT10 is present in the ER.

KEYWORDS:

Fe2+/2-oxoglutarate dependent dehydrogenases; GLUT10; arterial tortuosity syndrome; dehydroascorbic acid; endoplasmic reticulum; nuclear envelope

PMID:
28829359
PMCID:
PMC5578206
DOI:
10.3390/ijms18081820
[Indexed for MEDLINE]
Free PMC Article

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