Transferrin: Endocytosis and Cell Signaling in Parasitic Protozoa

Abstract

Iron is the fourth most abundant element on Earth and the most abundant metal in the human body. This element is crucial for life because almost all organisms need iron for several biological activities. This is the case with pathogenic organisms, which are at the vanguard in the battle with the human host for iron. The latest regulates Fe concentration through several iron-containing proteins, such as transferrin. The transferrin receptor transports iron to each cell that needs it and maintains it away from pathogens. Parasites have developed several strategies to obtain iron as the expression of specific transferrin receptors localized on plasma membrane, internalized through endocytosis. Signal transduction pathways related to the activation of the receptor have functional importance in proliferation. The study of transferrin receptors and other proteins with action in the signaling networks is important because these proteins could be used as therapeutic targets due to their specificity or to differences with the human counterpart. In this work, we describe proteins that participate in signal transduction processes, especially those that involve transferrin endocytosis, and we compare these processes with those found in T. brucei, T. cruzi, Leishmania spp., and E. histolytica parasites.

The Trypanosomal Transferrin Receptor of Trypanosoma Brucei—A Review

“…Key: E7/E6, heterodimeric transferrin receptor; ellipse with Fe, holo-transferrin; empty ellipse, apo-transferrin; FP, flagellar pocket; FL, flagellum; V, endo-and exocytotic vesicles; EN, endosome; LY, lysosome; CY, cytosol. The TfR-ligand complex is endocytosed via a clathrin-dependent pathway [12,96]. Invagination of clathrin-coated vesicles leads to internalization of the receptor-ligand complex and subsequent discharge into the intracellular tubular system [95,96].…”

“…bicarbonate or carbonate, and at a physiological serum pH range, serum transferrin can bind either mono-or di-ferric iron atoms, transforming from apo-(iron-free) to holo-(iron-laden) transferrin [3,11]. Though both lobes bind ferric iron (Fe 3+ ), there is a difference in binding capability as the Cterminal lobe binds Fe 3+ more tightly and releases it more slowly [12]. Mammalian serum Tf is expressed in the liver, central nervous system (CNS), reproductive organs, spleen, and kidneys [13].…”

Transferrin in fishes: A review article

“…Trasnferrin consists of a single polypeptide chain of about 700 amino acid residues organized into the C and N lobes, each consisting of two domains to which iron is coordinated [9][10][11]. The globular lobes are connected by a short helical section.…”

“…Cells take up iron bound to transferrin using transferrin R, thus, the biological function of the specific receptors is to bind transferrin on the cell surface and ingests it [11]. The transferrin R, which is expressed in all nucleated cells in the body, assists iron uptake into vertebrate cells through a cycle of endo and exocytosis of transferrin [17].…”

Reciprocal interactions between Leishmania and their microenvironments during infection in the sand fly gut and human macrophages

“…Furthermore, there is direct correlation between the quantity of stored calcium and increased virulence of Leishmania parasites during host infection [279,280]. The significant increase in the abundance of transferrin and serotransferrin in the exosomes from infected MDMs may also be important modulating exosome formation and secretion during infection as well [281].…”