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Caenorhabditis elegans P 5B ‐type ATPase CATP‐5 operates in polyamine transport and is crucial for norspermidine‐mediated suppression of RNA interference
Author(s) -
Heinick Alexander,
Urban Katja,
Roth Stefan,
Spies Danica,
Nunes Frank,
Phanstiel Otto,
Liebau Eva,
Lüersen Kai
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-135889
Subject(s) - caenorhabditis elegans , polyamine , rna interference , mutant , biology , microbiology and biotechnology , spermidine , biochemistry , atpase , wild type , rna , chemistry , gene , enzyme
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. Norsper‐midine 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.—Heinick, A., Urban, K., Roth, S., Spies, D., Nunes, F., Phanstiel IV, O., Liebau, E., Lüersen, K. Caenorhabditis elegans P5B‐type ATPase CATP‐5 operates in polyamine transport and is crucial for norspermidine‐mediated suppression of RNA interference. FASEB J . 24, 206–217 (2010). www.fasebj.org