RRC ID 46442
著者 Sherman TA, Rongali SC, Matthews TA, Pfeiffer J, Nehrke K.
タイトル Identification of a nuclear carbonic anhydrase in Caenorhabditis elegans.
ジャーナル Biochim Biophys Acta
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.
GENERAL SIGNIFICANCE:A classical αCA isoform is targeted exclusively to the nucleus where its activity may impact nuclear physiologic and pathophysiologic responses.
巻・号 1823(4)
ページ 808-17
公開日 2012-4-1
DOI 10.1016/j.bbamcr.2011.12.014
PII S0167-4889(12)00002-X
PMID 22245567
PMC PMC3314132
MeSH Animals Bicarbonates / pharmacology Biocatalysis / drug effects Caenorhabditis elegans / drug effects Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carbonic Anhydrases / genetics Carbonic Anhydrases / metabolism* Cell Nucleus / drug effects Cell Nucleus / enzymology* Exons / genetics Gene Expression Regulation, Enzymologic / drug effects Genome, Helminth / genetics Hydrogen-Ion Concentration / drug effects Isoenzymes / genetics Isoenzymes / metabolism Multigene Family Protein Transport / drug effects Recombinant Proteins / metabolism
IF 3.411
引用数 5
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm2805