title: Identification of a nuclear carbonic anhydrase in Caenorhabditis elegans.
abstract: BACKGROUND
  Carbonic anhydrases (CA) catalyze the inter-conversion of CO(2) with HCO(3) and H(+), and are involved in a wide variety of physiologic processes such as anion transport, pH regulation, and water balance. In mammals there are sixteen members of the classical α-type CA family, while the simple genetic model organism Caenorhabditis elegans codes for six αCA isoforms (cah-1 through cah-6).
  
  
  METHODS
  Fluorescent reporter constructs were used to analyze gene promoter usage, splice variation, and protein localization in transgenic worms. Catalytic activity of recombinant CA proteins was assessed using Hansson's histochemistry. CA's ability to regulate pH as a function of CO(2) and HCO(3) was measured using dynamic fluorescent imaging of genetically-targeted biosensors.
  
  
  RESULTS
  Each of the six CA genes was found to be expressed in a distinct repertoire of cell types. Surprisingly, worms also expressed a catalytically-active CA splice variant, cah-4a, in which an alternative first exon targeted the protein to the nucleus. Cah-4a expression was restricted mainly to the nervous system, where it was found in nearly all neurons, and recombinant CAH-4A protein could regulate pH in the nucleus.
  
  
  CONCLUSIONS
  In addition to establishing C. elegans as a platform for studying αCA function, this is the first example of a nuclear-targeted αCA in any organism to date.
  
  
  CONCLUSIONS
  A classical αCA isoform is targeted exclusively to the nucleus where its activity may impact nuclear physiologic and pathophysiologic responses.
authors.affiliation: Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Sherman
authors.forename: Sharath C
authors.initials: SC
authors.lastname: Rongali
authors.forename: Tori A
authors.initials: TA
authors.lastname: Matthews
authors.forename: Jason
authors.initials: J
authors.lastname: Pfeiffer
authors.forename: Keith
authors.initials: K
authors.lastname: Nehrke
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D055162:Biocatalysis / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology*; D005091:Exons / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D049751:Genome, Helminth / Q000235:genetics; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D021381:Protein Transport / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D001639:Bicarbonates; D029742:Caenorhabditis elegans Proteins; D007527:Isoenzymes; D011994:Recombinant Proteins; D002256:Carbonic Anhydrases