title: The exopolyphosphatase TbrPPX1 of Trypanosoma brucei.
abstract: BACKGROUND
  Exopolyphosphatases and pyrophosphatases play important but still incompletely understood roles in energy metabolism, and also in other aspects of cell biology such as osmoregulation or signal transduction. Earlier work has suggested that a human exopolyphosphatase, Prune, might exhibit cyclic nucleotide phosphodiesterase activity.
  
  
  RESULTS
  The kinetoplastida, a large order of unicellular eukaryotes that contains many important pathogens such as Trypanosoma brucei (human sleeping sickness), Trypanosoma cruzi (Chagas disease) or Leishmania ssp (several clinically dinstinct leishmaniases) all contain several exo- and pyrophosphatases. The current study provides a systematic classification of these enzymes, which now allows to situate the information that is already available on some of these enzymes. It then analyses the exopolyphosphatase TbrPPX1 of T. brucei in detail, using RNA interference and genetic knockouts in an attempt to define its function, and immunofluorescence microscopy to study its subcellular localization.TbrPPX1 is an exopolyphosphatase that does hydrolyze pentasodium triphosphate, but not organic triphosphates such as ATP, pyrophosphate or long-chain polyphosphates. Finally, the study investigates the potential cyclic nucleotide phosphodiesterase activity of TbrPPX1.
  
  
  CONCLUSIONS
  All kinetoplastid genomes that are currently available contain genes for an exopolyphosphatase and two classes of pyrophosphatases, one associated with the acidocalcisomes and one cytoplasmic. TbrPPX1 represents the T. brucei exopolyphosphatase. It is located throughout the cytoplasm, and its genetic ablation does not produce a dramatic phenotype. Importantly, TbrPPX1 does not exhibit any cyclic nucleotide specific phosphodiesterase activity, which definitively eliminates it as an additional player in cAMP signalling of the kinetoplastida.
authors.affiliation: Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH-3012 Bern, Switzerland.
authors.forename: Edith
authors.initials: E
authors.lastname: Luginbuehl
authors.forename: Stefan
authors.initials: S
authors.lastname: Kunz
authors.forename: Laurent
authors.initials: L
authors.lastname: Wentzinger
authors.forename: Florian
authors.initials: F
authors.lastname: Freimoser
authors.forename: Thomas
authors.initials: T
authors.lastname: Seebeck
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D005260:Female; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D018503:Genome, Protozoan; D051379:Mice; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000235:genetics*
chemical_list: D015800:Protozoan Proteins; D017766:Acid Anhydride Hydrolases; D011755:Pyrophosphatases; C020137:exopolyphosphatase