In a broadly based collaboration of Rainer Prohaska and his group with the group of Naomi Taylor (Montpellier / F) it was shown that the massive expression of the glucose transporter GLUT1 in erythrocytes is only found in humans, great apes and other mammals that have lost the ability to synthesize vitamin C due to a mutation in the enzyme GLO. GLUT1 is known to transport also dehydroascorbate (DHA), the oxidized form of vitamin C. Now, the GLUT1-interacting membrane protein stomatin is shown to act as a molecular switch depressing glucose and enhancing DHA uptake. Thus, erythrocyte-specific co-expression of GLUT1 with stomatin constitutes an evolutionary, compensatory mechanism in GLO-defective mammals leading to enhanced uptake of DHA and reduction to vitamin C.
Montel-Hagen A, Kinet S, Manel N, Mongellaz C, Prohaska R, Battini JL, Delaunay J, Sitbon M, Taylor N. Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C. Cell. 2008 Mar 21;132(6):1039-48. PMID: 18358815 Of all cells, human erythrocytes express the highest level of the Glut1 glucose transporter. However, the regulation and function of Glut1 during erythropoiesis are not known. Here, we report that glucose transport actually decreases during human erythropoiesis despite a >3-log increase in Glut1 transcripts. In contrast, Glut1-mediated transport of L-dehydroascorbic acid (DHA), an oxidized form of ascorbic acid (AA), is dramatically enhanced. We identified stomatin, an integral erythrocyte membrane protein, as regulating the switch from glucose to DHA transport. Notably though, we found that erythrocyte Glut1 and associated DHA uptake are unique traits of humans and the few other mammals that have lost the ability to synthesize AA from glucose. Accordingly, we show that mice, a species capable of synthesizing AA, express Glut4 but not Glut1 in mature erythrocytes. Thus, erythrocyte-specific coexpression of Glut1 with stomatin constitutes a compensatory mechanism in mammals that are unable to synthesize vitamin C.
Troadec MB, Kaplan J. Some vertebrates go with the GLO. Cell. 2008 Mar 21;132(6):921-2. PMID: 18358804 Most vertebrates synthesize vitamin C (ascorbate) de novo from glucose, but humans and certain other mammals cannot. In this issue, Montel-Hagen et al. (2008) demonstrate that erythrocytes from these ascorbate auxotrophs switch the preference of their glucose transporter Glut1 from glucose to dehydroascorbate (DHA), the oxidized form of vitamin C. This substrate preference switch is mediated by the membrane protein stomatin and is an evolutionary adaptation to vitamin C deficiency.