PROTEINS WITH GLYCOSYLPHOSPHATIDYLINOSITOL (GPI) SIGNAL SEQUENCES HAVE DIVERGENT FATES DURING A GPI DEFICIENCY - GPIS ARE ESSENTIAL FOR NUCLEAR DIVISION IN TRYPANOSOMA-CRUZI

Glycosylphosphatidylinositols (GPIs) are membrane anchors for cell sur face proteins of several major protozoan parasites of humans, includin g Trypanosoma cruzi, the causative agent of Chagas' disease, To invest igate the general role of GPIs in T. cruzi, we generated GPI-deficient parasites by heterologous expression of T. brucei GPI-phospholipase C . Putative protein-GPI intermediates were depleted, causing the bioche mical equivalent of a dominant-negative loss of function mutation in t he GPI pathway, Cell surface expression of major GPI-anchored proteins was diminished in GPI-deficient T. cruzi, Four proteins that are norm ally GPI-anchored in T. cruzi exhibited different fates during the GPI shortage; Ssp-Li and p75 were secreted prematurely, while protease gp 50/55 and p60 were degraded intracellularly. These observations demons trate that secretion and intracellular degradation of GPI-anchored pro teins may occur in the same genetic background during a GPI deficiency , We postulate that the interaction between a protein GPI transamidase and the COOH-terminal GPI signal sequence plays a pivotal role in det ermining the fate of these proteins, At a nonpermissive GPI deficiency , T. cruzi amastigotes inside mammalian cells replicated their single kinetoplast but failed at mitosis. Hence, in these protozoans, GPIs ap pear to be essential for nuclear division, but not for mitochondrial d uplication.