Publications

• The glucose-6-phosphate transporter is a phosphate-linked antiporter deficient in glycogen storage disease type Ib and Ic.

  Chen S.Y., Pan C.J., Nandigama K., Mansfield B.C., Ambudkar S.V., Chou J.Y.

  Glycogen storage disease type Ib (GSD-Ib) is caused by deficiencies in the glucose-6-phosphate (G6P) transporter (G6PT) that have been well characterized. Interestingly, deleterious mutations in the G6PT gene were identified in clinical cases of GSD type Ic (GSD-Ic) proposed to be deficient in an ... >> More

  Glycogen storage disease type Ib (GSD-Ib) is caused by deficiencies in the glucose-6-phosphate (G6P) transporter (G6PT) that have been well characterized. Interestingly, deleterious mutations in the G6PT gene were identified in clinical cases of GSD type Ic (GSD-Ic) proposed to be deficient in an inorganic phosphate (P(i)) transporter. We hypothesized that G6PT is both the G6P and P(i) transporter. Using reconstituted proteoliposomes we show that both G6P and P(i) are efficiently taken up into P(i)-loaded G6PT-proteoliposomes. The G6P uptake activity decreases as the internal:external P(i) ratio decreases and the P(i) uptake activity decreases in the presence of external G6P. Moreover, G6P or P(i) uptake activity is not detectable in P(i)-loaded proteoliposomes containing the p.R28H G6PT null mutant. The G6PT-proteoliposome-mediated G6P or P(i) uptake is inhibited by cholorgenic acid and vanadate, both specific G6PT inhibitors. Glucose-6-phosphatase-alpha (G6Pase-alpha), which facilitates microsomal G6P uptake by G6PT, fails to stimulate G6P uptake in P(i)-loaded G6PT-proteoliposomes, suggesting that the G6Pase-alpha-mediated stimulation is caused by decreasing G6P and increasing P(i) concentrations in microsomes. Taken together, our results suggest that G6PT has a dual role as a G6P and a P(i) transporter and that GSD-Ib and GSD-Ic are deficient in the same G6PT gene. << Less

  FASEB J 22:2206-2213(2008) [PubMed] [EuropePMC]

• SLC37A1 and SLC37A2 are phosphate-linked, glucose-6-phosphate antiporters.

  Pan C.J., Chen S.Y., Jun H.S., Lin S.R., Mansfield B.C., Chou J.Y.

  Blood glucose homeostasis between meals depends upon production of glucose within the endoplasmic reticulum (ER) of the liver and kidney by hydrolysis of glucose-6-phosphate (G6P) into glucose and phosphate (P(i)). This reaction depends on coupling the G6P transporter (G6PT) with glucose-6-phospha ... >> More

  Blood glucose homeostasis between meals depends upon production of glucose within the endoplasmic reticulum (ER) of the liver and kidney by hydrolysis of glucose-6-phosphate (G6P) into glucose and phosphate (P(i)). This reaction depends on coupling the G6P transporter (G6PT) with glucose-6-phosphatase-α (G6Pase-α). Only one G6PT, also known as SLC37A4, has been characterized, and it acts as a P(i)-linked G6P antiporter. The other three SLC37 family members, predicted to be sugar-phosphate:P(i) exchangers, have not been characterized functionally. Using reconstituted proteoliposomes, we examine the antiporter activity of the other SLC37 members along with their ability to couple with G6Pase-α. G6PT- and mock-proteoliposomes are used as positive and negative controls, respectively. We show that SLC37A1 and SLC37A2 are ER-associated, P(i)-linked antiporters, that can transport G6P. Unlike G6PT, neither is sensitive to chlorogenic acid, a competitive inhibitor of physiological ER G6P transport, and neither couples to G6Pase-α. We conclude that three of the four SLC37 family members are functional sugar-phosphate antiporters. However, only G6PT/SLC37A4 matches the characteristics of the physiological ER G6P transporter, suggesting the other SLC37 proteins have roles independent of blood glucose homeostasis. << Less

  PLoS ONE 6:E23157-E23157(2011) [PubMed] [EuropePMC]