Expression of SLC 4A11 protein in mouse and rat medulla: a candidate transporter involved in outer medullary ammonia recycling

Abstract

SLC 4A11 is a multifunctional membrane transporter involved with H + transport, NH 3 and alkaline pH stimulated H + transport, and water transport. The role of SLC 4A11 in the kidney is not well understood. A prior study has shown that in murine kidney, SLC 4A11/LacZ staining is primarily in the long‐looped descending thin limb ( DTL ) as determined by colocalization with aquaporin 1 ( AQP 1), a protein that is expressed in some, but not all, descending thin limb segments. Using a previously characterized polyclonal antibody, we demonstrate the selective expression of SLC 4A11 in the upper DTL s (which are AQP 1‐positive) in the outer medulla and inner medulla with little or no expression in the lower DTL s (which are AQP ‐1‐null). SLC 4A11 also colocalized with AQP 1 and the urea transporter UT ‐B in the mouse descending vasa recta, but was absent in mouse and rat ascending vasa recta. Mouse, but not rat, outer medullary collecting duct cells also labeled for SLC 4A11. Our results are compatible with the hypothesis that in the inner stripe of the outer medulla, SLC 4A11 plays a role in the countercurrent transport of ammonia absorbed from the outer medullary thick ascending limb and secreted into the long‐looped DTL s. SLC 4A11 can potentially modulate the rate of ammonia transport in the mouse outer medullary collecting duct. Our data suggest functionally unique SLC 4A11 pathways in mouse and rat and complement previous studies of DTL Na + , urea and water permeability indicating that the upper and lower DTL s of long‐looped nephrons are functionally distinct.

A comprehensive mouse kidney atlas enables rare cell population characterization and robust marker discovery

“… 40 Slc4a11 is known to be expressed in DTL cells, although expression has been described only in the medullary part of the kidney. 41 …”

The H+ Transporter SLC4A11: Roles in Metabolism, Oxidative Stress and Mitochondrial Uncoupling

“…Parents of CHED children who are heterozygous for SLC4A11 mutations also appear to be at risk of developing FECD [ 34 ]. No other human disorders have been definitively associated with SLC4A11; however, there are some reports from animal models that suggest kidney involvement (polyuria) [ 32 , 35 , 36 , 37 ] and submandibular gland dysfunction [ 38 ], which is consistent with the strong expression of SLC4A11 in these tissues.…”

“…Whether this is due to dysfunctional autophagy or lysosome production remains to be examined. SLC4A11 is expressed in the kidney medulla [ 32 , 36 ] and the knock-out yields urine hypo-osmolarity [ 32 , 35 ]. Based on anatomical location within the outer medulla, it is conceivable that SLC4A11 has a role in countercurrent ammonia transport [ 36 ].…”

“…SLC4A11 is expressed in the kidney medulla [ 32 , 36 ] and the knock-out yields urine hypo-osmolarity [ 32 , 35 ]. Based on anatomical location within the outer medulla, it is conceivable that SLC4A11 has a role in countercurrent ammonia transport [ 36 ]. There is high expression of SLC4A11 in mouse submandibular gland (SMG) diffusely localized in acinar and duct cells.…”

Mitochondrial Targeting of the Ammonia-Sensitive Uncoupler SLC4A11 by the Chaperone-Mediated Carrier Pathway in Corneal Endothelium

“…A study by Gee et al 54 showed the expression of Slc4a11 in the upper descending thin limbs of the mouse kidney, which was hypothesized as a transporter-modulating ammonia recycling in the outer medulla. Slc4a11 localization to kidney mitochondria and OCR analysis using isolated kidney mitochondria reveal similar characteristics of SLC4A11 as in corneal endothelium and transfected fibroblasts.…”