Endocytosis, signal transduction and proteolytic cleaving of human holotransferrin in Entamoeba histolytica. Issue 12 (October 2020)

• Record Type: Journal Article
• Authors: Reyes-López, Magda; Piña-Vázquez, Carolina; Pérez-Salazar, Eduardo; de la Garza, Mireya
• Is Part Of: International journal for parasitology. Volume 50:Issue 12(2020)
• Page Start: 959
• Page End: 967
• Publication Date: 2020-10
• Subjects: Entamoeba histolytica -- Transferrin -- Signal transduction -- Carbohydrate metabolism; Parasitology -- Periodicals; Parasitology -- Periodicals; Parasitologie -- Périodiques; Parasitology; Periodicals; Electronic journals; 571.999
• DOI: 10.1016/j.ijpara.2020.05.013
• Languages: English
• ISSNs: 0020-7519

Abstract

Graphical abstract: Highlights: Human holotransferrin (holoTf) is an iron-containing protein used by Entamoeba histolytica as an iron source. Entamoeba histolytica transferrin receptor (EhTfR) triggers the signal for parasite proliferation. HoloTf is endocytosed in clathrin-coated vesicles and travels via the endosomal-lysosomal system. Signal transduction goes to MAPK and FAK signalling pathways, involving the activation of other PI-3Ks. Proteins that respond to proliferation signals by holoTf are related to carbohydrate metabolism and cellular protection. Abstract: Amoebiasis is a parasitic infection of the human large intestine caused by Entamoeba histolytica ; this disease mainly affects people from developing countries. To survive, this primitive protozoan has a high demand for iron, and it uses host iron proteins upon invasion. Transferrin (Tf) is a plasma iron-binding protein that transports and delivers iron to all cells. Iron-loaded Tf (holoTf) in humans can support the proliferation of amoebae in vitro by binding to an amoebic TfR (EhTfR), and amoebae endocytose it inside clathrin-coated vesicles. In this study, it was found that EhTfR phosphorylation is required for human holoTf endocytosis by E. histolytica . Once this complex is endocytosed, human holoTf could be degraded with a nutritional purpose by cysteine proteases. HoloTf endocytosis initiates the activation of the mitogen-activated protein kinases (MAPKs) and focal adhesion kinase (FAK) pathways, which induce cell proliferation with phosphoinositide 3-kinase (PI-3 K) and Ca 2+ involvement. In the first minutes after holoTf is endocytosed, several proteins are phosphorylated including transketolase, enolase, L- myo -inositol-1-phosphate synthase and phosphoglucomutase, which control carbohydrate metabolism, and heat shock protein-70. The study of these proteins and their signal transduction pathways could be useful for developing future therapies.