Developmental Expression of a Trypanosoma cruzi Phosphoinositide-Specific Phospholipase C in Amastigotes and Stimulation of Host Phosphoinositide Hydrolysis

Abstract

ABSTRACT Phosphoinositide phospholipase C (PI-PLC) plays an essential role in cell signaling. A unique Trypanosoma cruzi PI-PLC ( Tc PI-PLC) is lipid modified in its N terminus and localizes to the outer surface of the plasma membrane of amastigotes. We show here that Tc PI-PLC is developmentally regulated in amastigotes and shows two peaks of surface expression during the developmental cycle of T. cruzi , the first immediately after differentiation of trypomastigotes into amastigotes and the second before differentiation of amastigotes into trypomastigotes. Surface expression of Tc PI-PLC coincides with phosphatidylinositol 4,5-bisphosphate (PIP 2 ) depletion in the host cell membrane and with an increase in the levels of its product, inositol 1,4,5-trisphosphate. During extracellular differentiation, PI-PLC is secreted into the incubation medium. Maximal early expression of Tc PI-PLC on the surface of amastigotes and PIP 2 depletion coincide with host cytoskeletal changes, Ca 2+ signaling, and transcriptional responses described previously. The presence of Tc PI-PLC on the outer surface of the plasma membrane of the parasite and the capacity to be secreted and to alter host phospholipids are novel mechanisms of the host-parasite interaction.