G protein-coupled receptors (GPCRs) are a large family of about 800 types of cell membrane receptors that play a crucial role in the transmission of signals from the external environment to the interior of cells. This is why they are the target of many drugs.
Now, a new study led from the University of Birmingham, UK, and with the participation of Jana Selent’s research group at the Hospital del Mar Medical Research Institute (IMIM), has revealed in detail the molecular mechanisms that explains how the cell’s response to stimuli is regulated by these receptors. In particular, thanks to the atomic-scale simulation tools provided by the IMIM team, the researchers have been able to demonstrate the dynamics of the GPCRs regulation by the beta arrestin protein. This protein binds to the intracellular part of GPCRs once they have been activated by an external stimulus, and modulates their action. The group led by Selent has been able to simulate how and for how long beta-arrestin interacts with the receptors.
“The interaction of beta-arrestin and active receptors is more dynamic than previously thought, allowing for a better control of the signals mediated by these receptors”.
Jana Selent (IMIM)
According to Tomasz Stepniewski and Brian Medel Lacruz, IMIM researchers who participated in the research, this finding shows that beta-arrestin could be a good target for both known and new drugs.
Indeed, as Jana Selent explains, GPCRs are involved in a wide range of biological processes, such as, for example:
- sensory perception (sight, taste and smell)
- signaling and hormonal regulation
- neurotransmission
- brain function
- inflammation
- cell adhesion
- pain perception
So much so that, currently, between 30 and 40% of existing drugs exert their effects on GPCRs. Therefore, knowing how arrestin controls these receptors opens new avenues of study for the improvement of known drugs or the design of new drugs that are more efficient and less toxic.
The knowledge gained from the new discovery could potentially be applied to any disease in which GPCRs are involved, for example, cardiovascular diseases (hypertension, heart failure), neurological disorders (Parkinson’s, Alzheimer’s, depression) or metabolic disorders (obesity, diabetes). In fact, the group led by Selent is already starting to work on a potential drug against schizophrenia. However, “it would be necessary to investigate the value of this strategy for each individual application,” clarifies the researcher.
