title: SLC22A13 catalyses unidirectional efflux of aspartate and glutamate at the basolateral membrane of type A intercalated cells in the renal collecting duct.
abstract: In vertebrates, SLC22A13 is an evolutionarily conserved transport protein of the plasma membrane. In humans and rat, it is principally expressed in the kidney. The precise localization and physiological function are unknown. In the present study, immunohistochemistry revealed that expression of SLC22A13 is confined to the basolateral membrane of type A intercalated cells in rat kidney. Double-staining confirmed that SLC22A13 co-localizes with anion exchanger 1. LC-MS difference shading showed that heterologous expression of human and rat SLC22A13 in HEK (human embryonic kidney)-293 cells stimulates efflux of guanidinosuccinate, aspartate, glutamate and taurine. Time courses of uptake of [3H]aspartate and [3H]glutamate revealed that SLC22A13 counteracted endogenous uptake. By contrast, OAT2 (organic anion transporter 2), a bidirectional glutamate transporter, increased accumulation of [3H]glutamate. Thus SLC22A13 catalyses unidirectional efflux. Velocity of efflux of standard amino acids was measured by LC-MS/MS. Expression of SLC22A13 strongly stimulated efflux of aspartate, taurine and glutamate. When the intracellular concentrations of aspartate and taurine were increased by pre-incubation, velocities of efflux increased linearly. We propose that in type A intercalated cells, SLC22A13 compensates luminal exit of protons by mediating the basolateral expulsion of the anions aspartate and glutamate. In this context, unidirectional efflux is essential to avoid anion re-entering. Loss of SLC22A13 function could cause distal tubular acidosis.
authors.affiliation: *Department of Pharmacology, University of Cologne, Gleueler Straße 24, 50931 Cologne, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schulz
authors.affiliation: *Department of Pharmacology, University of Cologne, Gleueler Straße 24, 50931 Cologne, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Fork
authors.affiliation: *Department of Pharmacology, University of Cologne, Gleueler Straße 24, 50931 Cologne, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Bauer
authors.affiliation: †Global Drug Discovery, Bayer Pharma AG, 42096 Wuppertal, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Golz
authors.affiliation: †Global Drug Discovery, Bayer Pharma AG, 42096 Wuppertal, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Geerts
authors.affiliation: *Department of Pharmacology, University of Cologne, Gleueler Straße 24, 50931 Cologne, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Schömig
authors.affiliation: *Department of Pharmacology, University of Cologne, Gleueler Straße 24, 50931 Cologne, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Gründemann
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002384:Catalysis; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000096:biosynthesis* / Q000235:genetics; D021381:Protein Transport / Q000502:physiology; D051381:Rats
chemical_list: D027361:Organic Anion Transporters; C530205:SLC22A13 protein, human; D001224:Aspartic Acid; D018698:Glutamic Acid