title: SLC37A1 and SLC37A2 are phosphate-linked, glucose-6-phosphate antiporters.
abstract: 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.
authors.affiliation: Section on Cellular Differentiation, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Chi-Jiunn
authors.initials: CJ
authors.lastname: Pan
authors.forename: Shih-Yin
authors.initials: SY
authors.lastname: Chen
authors.forename: Hyun Sik
authors.initials: HS
authors.lastname: Jun
authors.forename: Su Ru
authors.initials: SR
authors.lastname: Lin
authors.forename: Brian C
authors.initials: BC
authors.lastname: Mansfield
authors.forename: Janice Y
authors.initials: JY
authors.lastname: Chou
mesh_terms: D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017920:Antiporters; D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; D010710:Phosphates; D011510:Proteolipids; C569995:Slc37a2 protein, human; C111261:glucose 6-phosphate(transporter); C020485:proteoliposomes; D019298:Glucose-6-Phosphate; C036527:SLC37A1 protein, human; D005947:Glucose