Involvement of calyculin A-sensitive phosphatase(s) in the differentiation of Trypanosoma cruzi trypomastigotes to amastigotes

Mol Biochem Parasitol. 1999 Jan 25;98(2):239-52. doi: 10.1016/s0166-6851(98)00172-8.

Abstract

Differentiation of the non-dividing trypomastigote form of Trypanosoma cruzi, the causative agent of Chagas disease, to the dividing amastigote form normally occurs in cytoplasm of infected cells. Here we show that calyculin A. a potent inhibitor of protein phosphatases 1 and 2A, induces at pH 7.5 extracellular transformation of long slender trypomastigotes to round amastigote-like forms which acquire characteristic features observed after the normal differentiation process: repositioning and structural changes of the kinetoplast, release of surface neuraminidase, and expression of amastigote-specific epitopes. Calyculin A inhibits parasite phosphatases and changes in the phosphorylation of specific proteins occur during the transformation process. As an exposure of trypomastigotes to calyculin A concentrations as low as 1 nM and for only 1-2 h is sufficient to induce transformation, the inhibition of calyculin A-sensitive phosphatase(s) appears to play a major role in initiating the trypomastigote differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Protozoan / metabolism
  • Cell Differentiation
  • Membrane Proteins / metabolism
  • Neuraminidase / metabolism
  • Oxazoles / pharmacology*
  • Phosphoprotein Phosphatases / antagonists & inhibitors*
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Trypanosoma cruzi / drug effects
  • Trypanosoma cruzi / enzymology*
  • Trypanosoma cruzi / ultrastructure*

Substances

  • Antigens, Protozoan
  • Membrane Proteins
  • Oxazoles
  • calyculin A
  • Phosphoprotein Phosphatases
  • Neuraminidase