Entamoeba histolytica is a protozoan parasite that invades human intestine leading to ulceration and destruction of tissue. Amoebic movement and phagocytosis of human cells is accompanied by characteristic changes in cell morphology. Amoebae become polarized, developing a frontal pseudopod and a well-defined rear zone of membrane accumulation designated the uroid. In motile eukaryotic cells, a phenomenon that contributes to movement is the capping of receptors at the cell surface. During the capping process, E. histolytica concentrates ligand-receptor complexes in the uroid. Interestingly, some of these surface receptors are involved in the survival of the parasite. While looking for regulators of capping and uroid formation, we identified RacG, an E. histolytica protein that is homologous to human Rac1. This protein belongs to the Rac subfamily of small GTPases implicated in interactions between the actin cytoskeleton and the membrane of mammalian cells. Cloning of the EhracG gene and analysis of the protein activity either in murine fibroblasts or in E. histolytica revealed that EhRacG induces a characteristic Rac phenotype. When expressed in amoebae, an EhRacG-V12 mutant protein not only deregulated cell polarity, but also caused a defect in cytokinesis. Analysis of the cytoskeleton in amoebae bearing this mutant revealed that F-actin concentrated at the periphery of the cell. In addition, the number and localization of uroids were modified. These results suggest a role for EhRacG in amoebic morphogenesis and cytokinesis.

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