Evidence of G-Protein-Coupled Receptors (GPCR) in the Parasitic Protozoa Plasmodium falciparum-Sensing the Host Environment and Coupling within Its Molecular Signaling Toolkit

Abstract

Throughout evolution, the need for single-celled organisms to associate and form a single cluster of cells has had several evolutionary advantages. In complex, multicellular organisms, each tissue or organ has a specialty and function that make life together possible, and the organism as a whole needs to act in balance and adapt to changes in the environment. Sensory organs are essential for connecting external stimuli into a biological response, through the senses: sight, smell, taste, hearing, and touch. The G-protein-coupled receptors (GPCRs) are responsible for many of these senses and therefore play a key role in the perception of the cells' external environment, enabling interaction and coordinated development between each cell of a multicellular organism. The malaria-causing protozoan parasite, Plasmodium falciparum, has a complex life cycle that is extremely dependent on a finely regulated cellular signaling machinery. In this review, we summarize strong evidence and the main candidates of GPCRs in protozoan parasites. Interestingly, one of these GPCRs is a sensor for K⁺ shift in Plasmodium falciparum, PfSR25. Studying this family of proteins in P. falciparum could have a significant impact, both on understanding the history of the evolution of GPCRs and on finding new targets for antimalarials.

Keywords: GPCRs; Plasmodium falciparum; calcium; cell signaling; synchronization.

Figure 1

Schematic figure of the intraerythrocytic cycle of P. falciparum. Merozoites from the liver stages are released into the bloodstream and invade the erythrocytes, differentiating into rings. The ring stage grows in volume taking advantage of the abundance of nutrients until it becomes a trophozoite, at which stage the metabolic activity is high and DNA replication begins. The development is completed in the schizont stage, where it is possible to notice several nuclei that will later segment into new merozoites. The mature merozoites rupture the RBC and are released into the bloodstream ready to invade new cells and complete the cycle. A small portion of the merozoites that invade the cells differentiate into gametocytes, which, over 14 days, complete the development and are able to infect mosquitoes.