“I started this research in 1984, being part of one of the firt team that characterized these receptors (the metabotropic glutamate receptors) using pharmacological tools.”

First, because this is a review article on an interesting topic in the GPCR field, a field of interest to many scientists. Second, the information provided in this review summarizes a number of publications that point to the formation of dimers as a prerequisite for their activation. Since this question is still a matter of intense debate for the other GPCRs, this obviously is of interest to the entire GPCR community. Third, the receptors in this family include the GPCRs activated by the two main neurotransmitters (glutamate and GABA), the receptor for extracellular calcium (the mutation of which is responsible for genetic diseases), the receptor for the sweet and umami taste compounds, as well as some receptors for pheromones. Just this list shows how important are these receptors in terms of drug development both in the pharmaceutical and food industries. Last, these receptors are among the first GPCRs for which allosteric regulators have been identified by HTS, and as such, these receptors represent an excellent model to validate the use of such molecules in drug development.

This is a review article that describes specific features of a class of GPCRs, including recent information on their activation process as revealed by X-ray crystallography and mutagenesis studies.

Its significance is primarily as a reference for scientists interested in the activation process and pharmacology of class C GPCRs, and also for most scientists working on GPCRs.

As an author invited to prepare this review article, I obviously work in this field. I started this research in 1984, being a member of one of the first teams that characterized these receptors (the metabotropic glutamate receptors) using pharmacological tools. Since then, the activity of my team is dedicated to the detailed analysis of the activation process of these receptors—i.e., how do agonists stabilize the active state? How do antagonists prevent activation? Why are these receptors dimers? How can synthetic compounds allosterically regulate their activation process? How do they activate their main effector, the heterotrimeric G-proteins? This work is being conducted either on mGlu receptors or on the prototypic heterodimeric GPCR, the GABAB receptor.