Disease relevance of Car14

• We suggest that CA XIV is the target of CA inhibitors that enhance subretinal fluid absorption in macular edema [1].

High impact information on Car14

• To examine the relative importance of these two isozymes in this and other physiological functions attributed to extracellular CAs, we produced CA IV and CA XIV knockout (KO) mice by targeted mutagenesis and the doubly deficient CA IV/XIV KO mice by intercrossing the individual null mice [2].
• In addition, CA XIV is strongly expressed on retinal pigment epithelium (RPE) [1].
• This enrichment of CA XIV on specific membrane domains of glial cells and RPE suggests specialization for buffering pH and volume in retinal neurons and their surrounding extracellular spaces [1].
• The specific membrane domains that express CA XIV were endfoot and nonendfoot membranes on Muller cells and astrocytes and apical and basolateral membranes of RPE [1].
• Neither neurons nor capillary endothelial cells showed detectable labeling for CA XIV [1].

Biological context of Car14

• Full-length CA XIV is a transmembrane protein composed of an extracellular catalytic domain, a single transmembrane helix, and a short intracellular polypeptide segment [3].
• Here, we analyze the subcellular distribution of CA XIV in retina by high-resolution immunogold cytochemistry and show that the distribution in retina (on glial cells but not neurons) is different from that reported for brain (on neurons but not glia) [1].
• By Northern blot analysis, the gene expression of CA XIV is most abundant in the kidney and heart, followed by the skeletal muscle, brain, lung, and liver [4].
• CONCLUSIONS: The presence of CA XIV in the hepatocyte plasma membrane places this novel enzyme at a strategic site to control pH regulation and ion transport between the hepatocytes, sinusoids and bile canaliculi [5].

Anatomical context of Car14

• Therefore, the unique subcellular localization of CA IX and CA XIV in cardiac myocytes suggests different functions of both enzymes in excitation-contraction coupling [6].
• Thus, both CA IV and CA XIV contribute to extracellular buffering in the central nervous system, although CA IV appears to be more important in the hippocampus [2].
• In addition, CA XIV may facilitate CO(2) removal from neural retina and modulate photoreceptor function [1].
• The expression study of an epitope-tagged protein has suggested that CA XIV is located on the plasma membrane [4].
• When expressed in COS-7 cells, CA XIV exhibits CA activity that is predominantly associated with the membrane fraction [4].

Other interactions of Car14

• In the SL membrane, only CA IV and CA XIV are present [6].
• Isolation and characterization of CA XIV, a novel membrane-bound carbonic anhydrase from mouse kidney [4].
• The CA domain of CA XIV is highly homologous with those of known CAs, especially extracellular CAs including CA XII, IX, VI, and IV [4].
• Future studies will be necessary to assign functions to CA-II and CA-XIV in the mouse neural retina [7].
• We determined herein that CA-XIV, a approximately 45kDa membrane protein, is expressed in retina, as it is in kidney [7].

Analytical, diagnostic and therapeutic context of Car14

• The expression of CA XIV in the liver was confirmed by RT-PCR and western blotting [5].
• RT-PCR and western blotting were also performed for CA XIV [5].

References