Importance Of GTPases Research Articles

The Tail Domain of Entamoeba histolytica GEF : A Guanine Nucleotide Exchange Factor

Invasion of human tissues by Entamoeba histolytica involves a number of processes common to metastatic and phagocytic cells. The steps necessary for metastatic and amebic invasion include attachment to the target cell, adherence to molecules of the extracellular matrix (ECM), destruction of matrix molecules by proteolysis, and phagocytosis. During the invasion of human epithelia by virulent E. histolytica , the trophozoites are stimulated by external signals provided by the epithelium. Transduction of signals into the ameba is mediated by surface receptors (1). These receptors may trigger a signaling pathway regulated by different proteins, such as members of the Ras superfamily. Five small GTP binding proteins homologous to Rho family (2) and two Rac proteins (Rac A and Rac G) (3) have been detected in E. histolytica . Small GTPases are converted from the GDP-bound inactive form to the GTP-bound active form by a GDP/GTP exchange reaction regulated by a GDP/GTP exchange factor (GEF) (4). The importance of GTPases was first outlined when they were identified as key regulators of the actin cytoskeleton, signaling events ranging from cell adhesion, lymphocyte activation, motility, and transcription activation to cell cycle progression in higher eukaryotic cells. However, little is known about the physiological function of most GEFs. In this work, we report the identification of a candidate gene termed EhGEF from E. histolytica. It shows a strong homology to the faciogenital displasia gene, a putative Rho/Rac guanine nucleotide exchange factor (5).