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

Int J Mol Sci. 2017 Aug 22;18(8):1820. doi: 10.3390/ijms18081820.

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.

MeSH terms

  • Arteries / abnormalities*
  • Arteries / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Fibroblasts / metabolism*
  • Fluorescent Antibody Technique
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Humans
  • Intracellular Space / metabolism
  • Joint Instability / genetics
  • Joint Instability / metabolism*
  • Microsomes / metabolism
  • Protein Binding
  • Protein Transport
  • Skin Diseases, Genetic / genetics
  • Skin Diseases, Genetic / metabolism*
  • Vascular Malformations / genetics
  • Vascular Malformations / metabolism*

Substances

  • Glucose Transport Proteins, Facilitative
  • SLC2A10 protein, human

Supplementary concepts

  • Arterial Tortuosity Syndrome