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

PLoS One. 2011;6(9):e23157. doi: 10.1371/journal.pone.0023157. Epub 2011 Sep 20.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antiporters / genetics
  • Antiporters / metabolism*
  • Biological Transport
  • Blotting, Western
  • COS Cells
  • Chlorocebus aethiops
  • Endoplasmic Reticulum / metabolism*
  • Gene Expression Profiling
  • Glucose / metabolism
  • Glucose-6-Phosphate / metabolism
  • Glucose-6-Phosphate / pharmacokinetics
  • Humans
  • Intestinal Mucosa / metabolism
  • Kidney / metabolism
  • Liver / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Microscopy, Fluorescence
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism*
  • Pancreas / metabolism
  • Phosphates / metabolism*
  • Proteolipids / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Antiporters
  • Membrane Transport Proteins
  • Monosaccharide Transport Proteins
  • Phosphates
  • Proteolipids
  • Slc37a2 protein, human
  • glucose 6-phosphate(transporter)
  • proteoliposomes
  • Glucose-6-Phosphate
  • SLC37A1 protein, human
  • Glucose