Reference - Detail
|Author||Heinick A, Urban K, Roth S, Spies D, Nunes F, Phanstiel O 4th, Liebau E, Lüersen K.|
|Title||Caenorhabditis elegans P5B-type ATPase CATP-5 operates in polyamine transport and is crucial for norspermidine-mediated suppression of RNA interference.|
Physiological polyamines are required in various biological processes. In the current study, we used norspermidine, a structural analog of the natural polyamine spermidine, to investigate polyamine uptake in the model organism Caenorhabditis elegans. Norspermidine was found to have two remarkable effects: it is toxic for the nematode, without affecting its food, Escherichia coli; and it hampers RNA interference. By characterizing a norspermidine-resistant C. elegans mutant strain that has been isolated in a genetic screen, we demonstrate that both effects, as well as the uptake of a fluorescent polyamine-conjugate, depend on the transporter protein CATP-5, a novel P(5B)-type ATPase. To our knowledge, CATP-5 represents the first P(5)-type ATPase that is associated with the plasma membrane, being expressed in the apical membrane of intestinal cells and the excretory cell. Moreover, genetic interaction studies using C. elegans polyamine synthesis mutants indicate that CATP-5 has a function redundant to polyamine synthesis and link reduced polyamine levels to retarded postembryonic development, reduced brood size, shortened life span, and small body size. We suggest that CATP-5 represents a crucial component of the pharmacologically important polyamine transport system, the molecular nature of which has not been identified so far in metazoa.
|MeSH||Adenosine Triphosphatases / chemistry Adenosine Triphosphatases / classification Adenosine Triphosphatases / genetics Adenosine Triphosphatases / metabolism* Amino Acid Sequence Animals Animals, Genetically Modified Biological Transport, Active Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Escherichia coli / drug effects Escherichia coli / growth & development Gene Expression Genes, Helminth Membrane Proteins / chemistry Membrane Proteins / genetics Membrane Proteins / metabolism* Models, Molecular Molecular Sequence Data Polyamines / metabolism* RNA Interference / drug effects Recombinant Proteins / genetics Recombinant Proteins / metabolism Sequence Deletion Sequence Homology, Amino Acid Spermidine / analogs & derivatives Spermidine / metabolism Spermidine / toxicity|
|WOS Category||BIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY|