title: The betaine-GABA transporter (BGT1, slc6a12) is predominantly expressed in the liver and at lower levels in the kidneys and at the brain surface.
abstract: The Na(+)- and Cl(-)-dependent GABA-betaine transporter (BGT1) has received attention mostly as a protector against osmolarity changes in the kidney and as a potential controller of the neurotransmitter GABA in the brain. Nevertheless, the cellular distribution of BGT1, and its physiological importance, is not fully understood. Here we have quantified mRNA levels using TaqMan real-time PCR, produced a number of BGT1 antibodies, and used these to study BGT1 distribution in mice. BGT1 (protein and mRNA) is predominantly expressed in the liver (sinusoidal hepatocyte plasma membranes) and not in the endothelium. BGT1 is also present in the renal medulla, where it localizes to the basolateral membranes of collecting ducts (particularly at the papilla tip) and the thick ascending limbs of Henle. There is some BGT1 in the leptomeninges, but brain parenchyma, brain blood vessels, ependymal cells, the renal cortex, and the intestine are virtually BGT1 deficient in 1- to 3-mo-old mice. Labeling specificity was assured by processing tissue from BGT1-deficient littermates in parallel as negative controls. Addition of 2.5% sodium chloride to the drinking water for 48 h induced a two- to threefold upregulation of BGT1, tonicity-responsive enhancer binding protein, and sodium-myo-inositol cotransporter 1 (slc5a3) in the renal medulla, but not in the brain and barely in the liver. BGT1-deficient and wild-type mice appeared to tolerate the salt treatment equally well, possibly because betaine is one of several osmolytes. In conclusion, this study suggests that BGT1 plays its main role in the liver, thereby complementing other betaine-transporting carrier proteins (e.g., slc6a20) that are predominantly expressed in the small intestine or kidney rather than the liver.
authors.affiliation: Centre of Molecular Biology and Neuroscience, Dept. of Anatomy, Institute of Basic Medical Sciences, Univ. of Oslo, Oslo, Norway.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Holmseth
authors.forename: R
authors.initials: R
authors.lastname: Hua
authors.forename: A C
authors.initials: AC
authors.lastname: Lehre
authors.forename: A M
authors.initials: AM
authors.lastname: Olofsson
authors.forename: I
authors.initials: I
authors.lastname: Poblete-Naredo
authors.forename: S A
authors.initials: SA
authors.lastname: Kempson
authors.forename: N C
authors.initials: NC
authors.lastname: Danbolt
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D057809:HEK293 Cells; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007679:Kidney Medulla / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000502:physiology*; D008138:Loop of Henle / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D009997:Osmotic Pressure / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D000906:Antibodies; D050485:GABA Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C490439:Slc6a12 protein, mouse; D012965:Sodium Chloride