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

Differentiation of the non-dividing trypomastigote form of Trypanosoma cruz i, the causative agent of Chagas disease, to the dividing amastigote form n ormally 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 e xtracellular transformation of long slender trypomastigotes to round amasti gote-like forms which acquire characteristic features observed after the no rmal differentiation process: repositioning and structural changes of the k inetoplast, release of surface neuraminidase, and expression of amastigote- specific epitopes. Calyculin A inhibits parasite phosphatases and changes i n 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. (C) 1999 Elsevier S cience B.V. All rights reserved.