title: Induction and targeting of the glutamine transporter SN1 to the basolateral membranes of cortical kidney tubule cells during chronic metabolic acidosis suggest a role in pH regulation.
abstract: During chronic metabolic acidosis (CMA), the plasma levels of glutamine are increased and so is glutamine metabolism in the kidney tubule cells. Degradation of glutamine results in the formation of ammonium (NH(4)(+)) and bicarbonate (HCO(3)(-)) ions, which are excreted in the pre-urine and transported to the peritubular blood, respectively. This process contributes to counteract acidosis and to restore normal pH, but the molecular mechanism, the localization of the proteins involved and the regulation of glutamine transport into the renal tubular cells, remains unknown. SN1, a Na(+)- and H(+)-dependent glutamine transporter has previously been identified molecularly, and its mRNA has been detected in tubule cells in the medulla of the kidney. Now shown is the selective targeting of the protein to the basolateral membranes of the renal tubule cells of the S3 segment throughout development of the normal rat kidney. During CMA, SN1 expression increases five- to six-fold and appears also in cortical tubule cells in parallel with the increased expression and activity of phosphate-activated glutaminase, a mitochondrial enzyme involved in ammoniagenesis. However, SN1 remains sorted to the basolateral membranes. The unique ability of SN1 to change transport direction according to physiologic changes in transmembrane gradients of [glutamine] and pH and its sorting to the basolateral membranes and the presence of a putative pH responsive element in the 3' untranslated region (UTR) of the gene (supported here by the demonstration in CMA kidney of a protein that binds SN1 mRNA) are conducive to the function of this transporter in pH regulation.
authors.affiliation: Department of Anatomy and Centre for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, P.O. Box 1105 Blindern, University of Oslo, N-0317 Oslo, Norway.
authors.forename: Tom Tallak
authors.initials: TT
authors.lastname: Solbu
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Boulland
authors.forename: Wasim
authors.initials: W
authors.lastname: Zahid
authors.forename: May Kristin
authors.initials: MK
authors.lastname: Lyamouri Bredahl
authors.forename: Mahmood
authors.initials: M
authors.lastname: Amiry-Moghaddam
authors.forename: Jon
authors.initials: J
authors.lastname: Storm-Mathisen
authors.forename: Bjørg Ase
authors.initials: BA
authors.lastname: Roberg
authors.forename: Farrukh A
authors.initials: FA
authors.lastname: Chaudhry
mesh_terms: D000138:Acidosis / Q000378:metabolism* / Q000473:pathology; D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism*; D000818:Animals; D002908:Chronic Disease; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000254:growth & development / Q000378:metabolism; D007672:Kidney Cortex; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D009399:Nephrons / Q000378:metabolism; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D011522:Protons; C403222:system N protein 1