High capacity in G protein-coupled receptor signaling

Abstract

G protein-coupled receptors (GPCRs) constitute a large family of receptors that activate intracellular signaling pathways upon detecting specific extracellular ligands. While many aspects of GPCR signaling have been uncovered through decades of studies, some fundamental properties, like its channel capacity—a measure of how much information a given transmission system can reliably transduce—are still debated. Previous studies concluded that GPCRs in individual cells could transmit around one bit of information about the concentration of the ligands, allowing only for a reliable on or off response. Using muscarinic receptor-induced calcium response measured in individual cells upon repeated stimulation, we show that GPCR signaling systems possess a significantly higher capacity. We estimate the channel capacity of this system to be above two, implying that at least four concentration levels of the agonist can be distinguished reliably. These findings shed light on the basic principles of GPCR signaling.

Relevance of Hydrogen Bonds for the Histamine H2 Receptor-Ligand Interactions: A Lesson from Deuteration

“…Literature reports many studies on how GPCRs are activated and transmit their signals from the extracellular site through to the G protein coupling domain on the intracellular side [5]. Alternatively, we have been interested in how different ligands, agonists and antagonists, bind to the receptor binding site, and whether these processes are modulated upon deuteration, which could potentially reveal factors affecting receptor´s distinction between its agonists and antagonists.…”

Application of information theory in systems biology

“…The interpretation of the information depends on the problem settings involved in encode and decode systems. Keshelava et al (Keshelava et al 2018) repeatedly stimulated and measured the responses of single cells by using a live imaging technique, and evaluated the channel capacity at the single cell level. This varied between single cells, suggesting that the system of information transmission differs between individual cells.…”

“…Collecting quantitative data is generally more difficult for biochemical processes than for the electrical signals in neurons, and this has hampered the analysis of information processing in cells. However, recent developments in technology have made it possible to quantitatively measure various biochemical processes, and thus to investigate information processing, in a single cell (Cheong et al 2011;Gregor et al 2007;Keshelava et al 2018;Ozaki et al 2010;Selimkhanov et al 2014).…”

Intrinsic limits of information transmission in biochemical signalling motifs

“…Other studies have explored whether cells employ strategies to decrease the noise responsible for these seemingly low values (e.g. using dynamical trends as response to stimulus instead of a single point in time, or fold-change detection instead of concentration/copy number of chemical species) [10,[16][17][18][19], or if noisy responses can be useful for responses at the level of cellular populations instead of individual cells [15]. While these investigations have contributed greatly to our understanding of information transmission in specific cases, a full understanding of the general properties of information transmission in signalling networks have not yet been realized.…”

“…While these investigations have contributed greatly to our understanding of information transmission in specific cases, a full understanding of the general properties of information transmission in signalling networks have not yet been realized. For instance, the majority of signalling networks studied so far have estimated channel capacities ranging between 0.5 and 2.5 bits of information at the single-cell level [9,10,15,[17][18][19]. It is currently unclear if these values are indicative of all signalling networks or if 2.5 bits of information represents an intrinsic upper limit on intracellular information transmission [15].…”