Role of iso-receptors in receptor-receptor interactions with a focus on dopamine iso-receptor complexes

Abstract

<jats:title>Abstract</jats:title><jats:p>Intercellular and intracellular communication processes consist of signals and recognition/decoding apparatuses of these signals. In humans, the G protein-coupled receptor (GPCR) family represents the largest family of cell surface receptors. More than 30 years ago, it has been proposed that GPCR could form dimers or higher-order oligomers (receptor mosaics [RMs] at the plasma membrane level and receptor-receptor interactions [RRIs] have been proposed as a new integrative mechanism for chemical signals impinging on cell plasma membranes). The basic phenomena involved in RRIs are allostery and cooperativity of membrane receptors, and the present paper provides basic information concerning their relevance for the integrative functions of RMs. In this context, the possible role of iso-receptor RM is discussed (with a special focus on dopamine receptor subtypes and on some of the RMs they form with other dopamine iso-receptors), and it is proposed that two types of cooperativity, namely, homotropic and heterotropic cooperativity, could allow distinguishing two types of functionally different RMs. From a general point of view, the presence of iso-receptors and their topological organization within RMs allow the use of a reduced number of signals for the intercellular communication processes, since the target cells can recognize and decode the same signal in different ways. This theoretical aspect is further analyzed here by means of an analogy with artificial information systems. Thus, it is suggested that the ‘multiplexer’ and ‘demultiplexer’ concepts could, at least in part, model the role of RMs formed by iso-receptors in the information handling by the cell.</jats:p>

Allosteric modulation as a unifying mechanism for receptor function and regulation

“…Atomic force microscopy studies of rhodopsin have also revealed an oligomeric arrangement . There is also a wealth of biochemical evidence of cooperativity in the actions of orthosteric ligands of both class A and class B GPCRs suggesting that many GPCRs participate in oligomerization as part of their functional cycle, perhaps as a means of trafficking, compartmentalization or, for those receptors that are not obligate dimers, a means of dynamically regulating their selectivity or signaling efficiency …”

“…Interestingly, mutagenesis studies have also identified putative intracellular allosteric sites for synthetic modulators of some chemokine receptors, and novel lipidated peptides (“pepducins”) have been designed to specifically modulate the intracellular surfaces of different GPCRs . Finally, it is worth highlighting that there remain numerous pharmacological examples of GPCRs that display cooperativity in their modes of interaction with both cognate and synthetic ligands, suggesting that the potential for interactions across GPCR oligomeric arrays is also possible …”

Allosteric Modulation as a Unifying Mechanism for Receptor Function and Regulation

“…185 Finally, it is worth highlighting that there remain numerous pharmacological examples of GPCRs that display cooperativity in their modes of interaction with both cognate and synthetic ligands, suggesting that the potential for interactions across GPCR oligomeric arrays is also possible. 65,66…”

The multi-facet aspects of cell sentience and their relevance for the integrative brain actions: role of membrane protein energy landscape

“…According to our proposal, cell sentience is based not only on the ion entry into the cell cytoplasm across the plasma membrane ion channels, as suggested by Cook and coauthors, but also on the spontaneous activity of receptors especially of RMs (Fuxe and Agnati, 1985;Agnati et al, 1983Agnati et al, , 2016. These phenomena can likely have peculiar importance for the complex functions of multifunctional sensory nano-antenna carried out by the primary cilia (Handel et al, 1999;Brailov et al, 2000;Green et al, 2012).…”