title: The SLC37 family of phosphate-linked sugar phosphate antiporters.
abstract: The SLC37 family consists of four sugar-phosphate exchangers, A1, A2, A3, and A4, which are anchored in the endoplasmic reticulum (ER) membrane. The best characterized family member is SLC37A4, better known as the glucose-6-phosphate (G6P) transporter (G6PT). SLC37A1, SLC37A2, and G6PT function as phosphate (Pi)-linked G6P antiporters catalyzing G6P:Pi and Pi:Pi exchanges. The activity of SLC37A3 is unknown. G6PT translocates G6P from the cytoplasm into the lumen of the ER where it couples with either glucose-6-phosphatase-α (G6Pase-α) or G6Pase-β to hydrolyze intraluminal G6P to glucose and Pi. The functional coupling of G6PT with G6Pase-α maintains interprandial glucose homeostasis and the functional coupling of G6PT with G6Pase-β maintains neutrophil energy homeostasis and functionality. A deficiency in G6PT causes glycogen storage disease type Ib, an autosomal recessive disorder characterized by impaired glucose homeostasis, neutropenia, and neutrophil dysfunction. Neither SLC37A1 nor SLC37A2 can functionally couple with G6Pase-α or G6Pase-β, and there are no known disease associations for them or SLC37A3. Since only G6PT matches the characteristics of the physiological ER G6P transporter involved in blood glucose homeostasis and neutrophil energy metabolism, the biological roles for the other SLC37 proteins remain to be determined.
authors.affiliation: Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. chouja@mail.nih.gov
authors.forename: Janice Y
authors.initials: JY
authors.lastname: Chou
authors.forename: Hyun
authors.initials: H
authors.lastname: Sik Jun
authors.forename: Brian C
authors.initials: BC
authors.lastname: Mansfield
mesh_terms: D017920:Antiporters / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D005953:Glycogen Storage Disease Type I / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009004:Monosaccharide Transport Proteins / Q000172:deficiency / Q000378:metabolism; D005810:Multigene Family / Q000235:genetics*; D011487:Protein Conformation; D013403:Sugar Phosphates / Q000378:metabolism*
chemical_list: D017920:Antiporters; D009004:Monosaccharide Transport Proteins; C503531:SLC37A4 protein, human; D013403:Sugar Phosphates; D005947:Glucose