G protein signaling in the parasite Entamoeba histolytica

The parasite Entamoeba histolytica causes amebic colitis and systemic amebiasis. Among the known amebic factors contributing to pathogenesis are signaling pathways involving heterotrimeric and Ras superfamily G proteins. Here, we review the current knowledge of the roles of heterotrimeric G protein subunits, Ras, Rho and Rab GTPase families in E. histolytica pathogenesis, as well as of their downstream signaling effectors and nucleotide cycle regulators. Heterotrimeric G protein signaling likely modulates amebic motility and attachment to and killing of host cells, in part through activation of an RGS-RhoGEF (regulator of G protein signaling–Rho guanine nucleotide exchange factor) effector. Rho family GTPases, as well as RhoGEFs and Rho effectors (formins and p21-activated kinases) regulate the dynamic actin cytoskeleton of E. histolytica and associated pathogenesis-related cellular processes, such as migration, invasion, phagocytosis and evasion of the host immune response by surface receptor capping. A remarkably large family of 91 Rab GTPases has multiple roles in a complex amebic vesicular trafficking system required for phagocytosis and pinocytosis and secretion of known virulence factors, such as amebapores and cysteine proteases. Although much remains to be discovered, recent studies of G protein signaling in E. histolytica have enhanced our understanding of parasitic pathogenesis and have also highlighted possible targets for pharmacological manipulation. To better understand how the parasitic amoeba Entamoeba histolytica causes disease, examining a ubiquitous family of cellular signaling proteins has proved useful, according to a recent review by David Siderovski of the West Virginia University School of Medicine, USA. Entamoeba histolytica causes intestinal disease and can lead to fatal liver abscesses; infection rates can reach 50% in regions with limited access to clean drinking water. In E. histolytica, the G- protein family —proteins that typically regulate cell division and cellular scaffolding, or the cytoskeleton — is exceptionally large. These proteins also play many roles in pathogenicity, including immune system evasion, host cell attachment, and virulence factor secretion. G- proteins protein-coupled receptors are also commonly used as drug targets. Further research into G- protein signal transmission, and ways to interrupt it, may thus open the way for research into new pharmaceutical treatments.