Molecular Mechanisms of G Protein-Independent Signaling Mediated by 7-Transmembrane Receptors

Receptors of the 7-TMR group (G protein-coupled receptors, GPCRs) are uniquely important from the fundamental physiological aspect because they mediate the effects of a majority of the known neuromediators and hormones. According to a widely accepted paradigm, activation of heterotrimetric G proteins is the initial step in the process of transduction of signals from these receptors to effectors. In recent times, increasing proof of the existence of G protein-independent mechanisms providing initiation of biochemical signals by these receptors and modulation of the excitability of the neurons has been accumulated. According to these data, 7-TMRs are able to interact with a few cytoplasmic scaffold proteins and take part in various protein-to-protein interactions. Despite the fact that functional importance of many such interactions remains unknown at present, the respective results indicate that the above processes are capable not only of providing G protein-independent transmission of signals from the 7-TMRs, but also of influencing pharmacological characteristics, cellular localization, and compartmentalization of the mentioned receptors.