Abstract
The discovery that receptors from all families can establish allosteric receptor–receptor interactions and variably associate to form receptor complexes operating as integrative input units endowed with a high functional and structural plasticity has expanded our understanding of intercellular communication. Regarding the nervous system, most research in the field has focused on neuronal populations and has led to the identification of many receptor complexes representing an important mechanism to fine-tune synaptic efficiency. Receptor–receptor interactions, however, also modulate glia–neuron and glia–glia intercellular communication, with significant consequences on synaptic activity and brain network plasticity. The research on this topic is probably still at the beginning and, here, available evidence will be reviewed and discussed. It may also be of potential interest from a pharmacological standpoint, opening the possibility to explore, inter alia, glia-based neuroprotective therapeutic strategies.
Highlights
More than 4% of the human genome encodes cell receptors [1], which are presently organized into different families including intracellular receptors, matrix receptors, ligand- and voltage-gated ion channels, enzyme-linked receptors and G protein-coupled receptors (GPCRs)
It is well known that GPCR monomers can recognize and decode a variety of signals [5,6,7] and are endowed with an intrinsic plasticity, as GPCR activation can lead to different transduction patterns, such as G protein and/or arrestin pathways [8,9]
Oligomers further increased when biophysical techniques capable of detecting the spatial proximity of protein molecules became available [28,29]. These findings demonstrated that GPCRs can signal both as monomers and as part of receptor complexes and indicated that oligomeric organization represents a quite common feature in the different receptor families, with the ion channel receptors lying at one end of the spectrum and GPCRs at the other [30]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In the years that followed, direct evidence for the existence of this structural organization was provided by several groups [17,18,19,20,21,22,23,24,25,26,27], and the amount of data supporting the existence of GPCR oligomers further increased when biophysical techniques capable of detecting the spatial proximity of protein molecules became available [28,29] These findings demonstrated that GPCRs can signal both as monomers and as part of receptor complexes and indicated that oligomeric organization represents a quite common feature in the different receptor families, with the ion channel receptors (where multimerization is needed) lying at one end of the spectrum and GPCRs at the other [30]. After a brief recapitulation of the basic aspects concerning the structural biology of receptor complexes and their signaling, the available data on the role RRI play in the intercellular communication involving glial cells will be the focus of the present review article
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