The Glut1 and Glut4 glucose transporters are differentially expressed during perinatal and postnatal erythropoiesis

Abstract

Glucose is a major source of energy for living organisms, and its transport in vertebrates is a universally conserved property. Of all cell lineages, human erythrocytes express the highest level of the Glut1 glucose transporter with more than 200 000 molecules per cell. However, we recently reported that erythrocyte Glut1 expression is a specific trait of vitamin C-deficient mammalian species, comprising only higher primates, guinea pigs, and fruit bats. Here, we show that in all other tested mammalian species, Glut1 was transiently expressed in erythrocytes during the neonatal period. Glut1 was up-regulated during the erythroblast stage of erythroid differentiation and was present on the vast majority of murine red blood cells (RBCs) at birth. Notably though, Glut1 was not induced in adult mice undergoing anemia-induced erythropoiesis, and under these conditions, the up-regulation of a distinct transporter, Glut4, was responsible for an increased glucose transport. Sp3 and Sp1 transcriptions factors have been proposed to regulate Glut1 transcription, and we find that the concomitant repression of Glut1 and induction of Glut4 was associated with a significantly augmented Sp3/Sp1 ratio. IntroductionAnimals are heterotrophic, and most use sugar as their principal source of carbon. The facilitated diffusion of monosaccharides across the plasma membrane is mediated by specialized transporter molecules. The superfamily of related Glut sugar transporters comprises 14 identified isoforms in the human genome, all adopting a 12-membrane-spanning domain structure that delineate 6 extracellular loops. 1 These Glut isoforms are characterized by a moderate binding affinity and a rapid rate of sugar transport. 2 The first identified protein of this family, Glut1, is the main functional transporter of glucose in human erythrocytes and lymphocytes as well as the vast majority of transformed cell lines. 1,[3][4][5] Moreover, Glut1 also transports L-dehydroascorbic acid (DHA), the 2-electron oxidized intermediate of ascorbic acid, in various cell types. [6][7][8][9][10] Of all cell lineages, the human erythrocyte expresses the highest level of the Glut1 transporter, harboring more than 200 000 molecules per cell. Moreover, in the context of the red cell membrane, Glut1 accounts for 10% of the total protein mass. 5,11 We recently found that although both glucose and DHA are transported by Glut1 in human erythrocytes, [12][13][14] there is a preferential uptake of DHA in these cells. 15 The fact that Glut1 structure is conserved between mammals, birds, and fish indicates that the main features characterizing transport by this superfamily were established at an early phase of vertebrate evolution. 10 However, our experiments revealed erythrocyte Glut1 to be unique to those few mammalian species unable to synthesize ascorbic acid from glucose 15 (comprising humans, other higher primates, guinea pigs, and fruit bats), strongly suggesting that this feature constitutes a compensatory mechanism specific to mammals that are unable to syn...

The water channel aquaporin-1 partitions into exosomes during reticulocyte maturation: implication for the regulation of cell volume

“…A recent study showed that Glut-1 is not expressed by adult murine red cells, where it is replaced by Glut-4. 31 We infer that in adult mice the total pool of Glut-4 is down-regulated by its loss in exosomes, whereas in newborn animals, glucose transport regulation is linked to Glut-1 turnover and transcriptional switching to Glut-4. The fact that CD47 is also associated with exosomes is intriguing.…”

Myths, Artifacts, and Fatal Flaws: Identifying Limitations and Opportunities in Vitamin C Research

“…By contrast, mice lose GLUT1 during maturation, and GLUT4 is the predominant glucose transporter expressed in adult mouse erythrocytes [96]. GLUT4, by contrast, has diminished capacity to transport dehydroascorbic acid [97], which is reflected in the transport capacity of murine erythrocytes [78].…”

Developmental changes in the expression of the GLUT2 and GLUT4 genes in the longissimus dorsi muscle of Yorkshire and Tibetan pigs

“…To date, at least 14 family members have been identified in mammals, and these have similar structures but different tissue-and cell-specific distributions. GLUT2 and GLUT4 are two of the most important members of the family (Macheda et al, 2005;Montel-Hagen et al, 2008). GLUT2, which has a low affinity for glucose, is mainly expressed in the basolateral membrane of hepatocytes, the kidney, the small intestine, and insulin-producing β cells, and it plays a more permissive role in glucose catabolism (Roncero et al, 2004).…”