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.
Highlights
Throughout evolution, the need for single-celled organisms to associate and form a single cluster of cells has had several evolutionary advantages
Some 40% of all drugs found on the pharmaceutical market have a G-protein-coupled receptors (GPCRs) family member as a target, which reflects the importance of these proteins in cellular functions [3,4]
In a screening with compounds derived from 1,2,3-triazoles, Santos et al (2020) identified thirty-one compounds with antimalarial activity in the micromolar range, using wild P. falciparum strains. They were tested in a knockout strain for PfSR25, confirming the results found previously: the wild-type strain shows a higher IC50 for antimalarials than the PfSR25 knockout strain [66]
Summary
G-protein-coupled receptors (GPCRs) have a common core of seven successive transmembrane domains (7TM) linked by three extra and intracellular loops, conserved among eukaryotes [1]. Agonist, binds to a GPCR on the extracellular side, causing a conformational change mainly of the transmembrane helix 6 of the receptor, the signal is transmitted to the heterotrimeric G protein. These receptors do not act in a bimodal manner, and the signal can be activated at several intensities that result in several different signal results [5,6]. An activated GPCR-bound GDP free Gα subunit binds to soluble GTP, since its cytoplasmatic concentration is high, causing a conformational change that dissociates the heterotrimeric G protein into free Gα and Gβγ [14,15]. Β-arrestin physically blocks the binding of G proteins in an activated GPCR, and promotes clathrin-dependent internalization, interrupting stimulus and signal transduction [21,24]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
