SLC22A13 catalyzes unidirectional efflux of aspartate and glutamate at the basolateral membrane of type A intercalated cells in renal collecting duct

In vertebrates, SLC22A13 is an evolutionarily conserved transport protein of the plasma membrane. In human and rat, it is principally expressed in the kidney. The precise localization and physiological function are unknown. Here, 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 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, a bidirectional glutamate transporter, increased accumulation of 3H-glutamate. Thus, SLC22A13 catalyzes 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 preincubation, 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 reentering. Loss of SLC22A13 function could cause distal tubular acidosis.

Source: BJ Cell - October 23, 2013 Category: Biochemistry Authors: C Schulz, C Fork, T Bauer, S Golz, A Geerts, E Schömig, D Gründemann Tags: BJ Metabolism Source Type: research