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

Int J Mol Sci. 2021 Nov 17;22(22):12381. doi: 10.3390/ijms222212381.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antimalarials / pharmacology
  • Antimalarials / therapeutic use
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Host-Parasite Interactions / physiology*
  • Humans
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / metabolism*
  • Malaria, Falciparum / parasitology
  • Molecular Targeted Therapy / methods
  • Perception / drug effects
  • Perception / physiology*
  • Plasmodium falciparum / metabolism*
  • Protein Binding
  • Protozoan Proteins / metabolism*
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Antimalarials
  • Protozoan Proteins
  • Receptors, G-Protein-Coupled
  • Calcium