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

• Published in: International journal of molecular sciences Vol. 18; no. 8; p. 1820
• Main Authors: Gamberucci, Alessandra, Marcolongo, Paola, Németh, Csilla E, Zoppi, Nicoletta, Szarka, András, Chiarelli, Nicola, Hegedűs, Tamás, Ritelli, Marco, Carini, Giulia, Willaert, Andy, Callewaert, Bert L, Coucke, Paul J, Benedetti, Angiolo, Margittai, Éva, Fulceri, Rosella, Bánhegyi, Gábor, Colombi, Marina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.08.2017; MDPI
• Subjects: arterial tortuosity syndrome; Arteries - abnormalities; Arteries - metabolism; Decoration; dehydroascorbic acid; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Fe2+/2-oxoglutarate dependent dehydrogenases; Fibroblasts; Fibroblasts - metabolism; Fluorescent Antibody Technique; Glucose Transport Proteins, Facilitative - metabolism; GLUT10; Humans; Immunoblotting; Immunofluorescence; Intracellular Space - metabolism; Joint Instability - genetics; Joint Instability - metabolism; Liver; Localization; Microsomes - metabolism; Mitochondria; Mutation; nuclear envelope; Polyols; Protein Binding; Protein disulfide-isomerase; Protein Transport; Skin Diseases, Genetic - genetics; Skin Diseases, Genetic - metabolism; Sugar; Tortuosity; Vascular Malformations - genetics; Vascular Malformations - metabolism; nuclear envelope; dehydroascorbic acid; GLUT10; Fe2+/2-oxoglutarate dependent dehydrogenases; endoplasmic reticulum; arterial tortuosity syndrome
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18081820

GLUT10 belongs to a family of transporters that catalyze the uptake of sugars/polyols by facilitated diffusion. Loss-of-function mutations in the 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.