Transferrin: Endocytosis and Cell Signaling in Parasitic Protozoa

Figure 1

Transferrin endocytosis and signaling pathways in protozoan parasites. (A) Trafficking and insertion of membrane vesicles. The Tf-TfR complex is endocytosed in clathrin coated vesicles in T. brucei and E. histolytica but in noncoated vesicles in T. cruzi. The monomeric G proteins, Rabs, play a role in controlling the trafficking and insertion of new vesicles into endosomes or with endocytic recycling endosomes (ERCs) that recycle the receptor in T. brucei and Leishmania; in the case of T. cruzi, the receptor is not recycled back to the membrane. (B) Inositol-1,4,5-triphosphate and diacylglycerol signaling pathway. In T. brucei and Leishmania, TfR activation stimulates the formation of InsP3 and DAG through the action of GPI-PLC. Insp3 produces Ca²⁺ release from the endoplasmic reticulum to stimulate cell proliferation. Ca²⁺ in the cytoplasm binds to calmodulin (CaM) and translocates into the nucleus. DAG activates PKC, which then phosphorylates proteins that generate a specific response. (C) MAPK signaling pathway. TfR activated by Tf binding results in phosphorylation of MAPK, which has a central role in cell proliferation, and phosphorylation of the ERK1/2 kinases, which then translocate into the nucleus to activate transcription factors. These types of kinases are described in E. histolytica, T. brucei, and Leishmania. (D) Growth factor signaling pathway through TOR. Active PI3K takes information to TOR complexes that regulate protein synthesis by phosphorylation. TOR kinase functions are well conserved in eukaryotes with some differences in cellular localization in T. brucei and T. cruzi.