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
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, 1094 Budapest, Hungary.
Int J Mol Sci. 2017 Aug 22;18(8):1820. 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.
葡萄糖转运蛋白10（GLUT10）属于一类通过易化扩散催化糖类/多元醇摄取的转运蛋白家族。编码GLUT10的基因功能丧失突变是动脉迂曲综合征（ATS）的病因。由于该转运蛋白的亚细胞分布尚不明确，我们旨在阐明GLUT10的定位。计算机模拟的GLUT10定位预测表明其存在于内质网（ER）中。免疫印迹显示GLUT10蛋白存在于人类成纤维细胞和肝组织的微粒体部分，而线粒体部分则未检测到。免疫荧光显示，在人类成纤维细胞中，GLUT10呈现均匀的胞质分布，并在核周有强烈的标记，而线粒体标记物则显示出完全不同的标记模式。三名ATS患者的成纤维细胞中完全没有GLUT10标记。在一名ATS患者的成纤维细胞中外源表达带标签的GLUT10，结果显示其与内质网标记蛋白二硫键异构酶（PDI）严格共定位。结果表明GLUT10存在于内质网中。
