title: Membrane associated carbonic anhydrase IV (CA IV): a personal and historical perspective.
abstract: Carbonic anhydrase IV is one of 12 active human isozymes and one of four expressed on the extracellular surfaces of certain endothelial and epithelial cells. It is unique in being attached to the plasma membrane by a glycosyl-phosphatiydyl-inositol (GPI) anchor rather than by a membrane-spanning domain. It is also uniquely resistant to high concentrations of sodium dodecyl sulfate (SDS), which allows purification from tissues by inhibitor affinity chromatography without contamination by other isozymes. This unique resistance to SDS and recovery following denaturation is explained by the two disulfide bonds. The 35-kDa human CA IV is a "high activity" isozyme in CO2 hydration activity, like CA II, and has higher activity than other isozymes in catalyzing the dehydration of HCO3 (-). Human CA IV is also unique in that it contains no oligosaccharide chains, where all other mammalian CA IVs are glycoproteins with one to several oligosaccharide side chains.Although CA IV has been shown to be active in mediating CO2 and HCO3 (-) transport in many important tissues like kidney and lung, and in isolated cells from brain and muscle, the gene for CA IV appears not to be essential. The CA IV knockout mouse produced by targeted mutagenesis, though slightly smaller and produced in lower than expected numbers, is viable and has no obvious mutant phenotype. Conversely, several dominant negative mutations in humans are associated with one form of reitinitis pigmentosa (RP-17), which we attribute to unfolded protein accumulation in the choreocapillaris, leading to apoptosis of cells in the overlying retina.
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University, School of Medicine, St. Louis, MO, USA, waheeda@slu.edu.
authors.forename: Abdul
authors.initials: A
authors.lastname: Waheed
authors.forename: William S
authors.initials: WS
authors.lastname: Sly
mesh_terms: D000818:Animals; D030741:Carbonic Anhydrase IV / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D002384:Catalysis; D004795:Enzyme Stability; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D007527:Isoenzymes; D030741:Carbonic Anhydrase IV; C548247:CA4 protein, human