Carbonic anhydrase XIV: Luminal expression suggests key role in renal acidification

Abstract

Carbonic anhydrase (CA) plays a fundamental role in regulation of systemic acid-base homeostasis by facilitating urinary acidification. Four CA isozymes (CA II, IV, XII, XIV) have been identified in kidney. Until now, luminal CA IV, a GPI-anchored isozyme, was thought to mediate most bicarbonate absorption. Although CA XIV mRNA has been demonstrated in mouse and human kidney, the localization of this newly discovered CA has not been established. RT-PCR and Western blot analyses were used to demonstrate CA XIV mRNA and protein in extracts of cortex and medulla of mouse kidney. Polyclonal antibodies against mouse CA XIV were utilized for immunofluorescence to examine the pattern of expression of CA XIV in the nephron of both rat and mouse kidney. Immunofluorescence staining showed abundant expression of CA XIV in apical plasma membranes of the S1 and S2 segments of proximal tubules, and weaker staining in the basolateral membranes. Also, strong staining was seen in the initial portion of the thin descending limb of Henle. These results show that luminal CA XIV is strongly expressed in regions of the rodent nephron that have been thought to be important in urinary acidification. Staining for CA XIV and CA IV in the same sections showed some areas of co-expression, but also some areas where each was expressed without the other. Luminal CA XIV may account for a substantial fraction of the bicarbonate reabsorption previously attributed to CA IV. If so, CA XIV and CA IV may be functionally redundant.