scholarly journals Receptor–Receptor Interactions and Glial Cell Functions with a Special Focus on G Protein-Coupled Receptors

2021 ◽  
Vol 22 (16) ◽  
pp. 8656
Author(s):  
Diego Guidolin ◽  
Cinzia Tortorella ◽  
Manuela Marcoli ◽  
Chiara Cervetto ◽  
Guido Maura ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Brain Network ◽  
Synaptic Activity ◽  
Special Focus ◽  
Neuronal Populations ◽  
Cell Functions ◽  
Receptor Complexes ◽  
Receptor Interactions ◽  
G Protein Coupled ◽  
Fine Tune

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.

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

2018 ◽  
Vol 29 (7) ◽  
pp. 703-726 ◽  
Author(s):  
Diego Guidolin ◽  
Manuela Marcoli ◽  
Cinzia Tortorella ◽  
Guido Maura ◽  
Luigi F. Agnati
Keyword(s):  
G Protein ◽  
Intercellular Communication ◽  
Spatial Arrangement ◽  
Target Cells ◽  
Macromolecular Assemblies ◽  
Receptor Complexes ◽  
Allosteric Interactions ◽  
Receptor Interactions ◽  
And Function ◽  
G Protein Coupled

Abstract The proposal of receptor-receptor interactions (RRIs) in the early 1980s broadened the view on the role of G protein-coupled receptors (GPCR) in the dynamics of the intercellular communication. RRIs, indeed, allow GPCR to operate not only as monomers but also as receptor complexes, in which the integration of the incoming signals depends on the number, spatial arrangement, and order of activation of the protomers forming the complex. The main biochemical mechanisms controlling the functional interplay of GPCR in the receptor complexes are direct allosteric interactions between protomer domains. The formation of these macromolecular assemblies has several physiologic implications in terms of the modulation of the signaling pathways and interaction with other membrane proteins. It also impacts on the emerging field of connectomics, as it contributes to set and tune the synaptic strength. Furthermore, recent evidence suggests that the transfer of GPCR and GPCR complexes between cells via the exosome pathway could enable the target cells to recognize/decode transmitters and/or modulators for which they did not express the pertinent receptors. Thus, this process may also open the possibility of a new type of redeployment of neural circuits. The fundamental aspects of GPCR complex formation and function are the focus of the present review article.

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

2016 ◽  
Vol 27 (1) ◽  
pp. 1-25 ◽  
Author(s):  
Luigi F. Agnati ◽  
Diego Guidolin ◽  
Chiara Cervetto ◽  
Dasiel O. Borroto-Escuela ◽  
Kjell Fuxe
Keyword(s):  
Plasma Membranes ◽  
Membrane Receptors ◽  
General Point ◽  
Target Cells ◽  
Special Focus ◽  
Receptor Subtypes ◽  
Receptor Complexes ◽  
Communication Processes ◽  
Receptor Interactions

AbstractIntercellular 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.

scholarly journals Structural studies of phosphorylation-dependent interactions between the V2R receptor and arrestin-2

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qing-Tao He ◽  
Peng Xiao ◽  
Shen-Ming Huang ◽  
Ying-Li Jia ◽  
Zhong-Liang Zhu ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Conformational Changes ◽  
Nmr Spectrum ◽  
H Nmr ◽  
Interaction Sites ◽  
Receptor Interactions ◽  
Remote Sites ◽  
Genetic Code Expansion ◽  
G Protein Coupled ◽  
Interaction Change

AbstractArrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and 1H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions.

scholarly journals Bystander Attenuation of Neuronal and Astrocyte Intercellular Communication by Murine Cytomegalovirus Infection of Glia

2007 ◽  
Vol 81 (13) ◽  
pp. 7286-7292 ◽  
Author(s):  
Winson S. C. Ho ◽  
Anthony N. van den Pol
Keyword(s):  
Intercellular Communication ◽  
Neuronal Development ◽  
Primary Cultures ◽  
Synaptic Activity ◽  
Murine Cytomegalovirus ◽  
Intercellular Signaling ◽  
Mcmv Infection ◽  
High Potassium ◽  
Infected Cells ◽  
The Brain

ABSTRACT Astrocytes are the first cells infected by murine cytomegalovirus (MCMV) in primary cultures of brain. These cells play key roles in intercellular signaling and neuronal development, and they modulate synaptic activity within the nervous system. Using ratiometric fura-2 digital calcium imaging of >8,000 neurons and glia, we found that MCMV-infected astrocytes showed an increase in intracellular basal calcium levels and an enhanced response to neuroactive substances, including glutamate and ATP, and to high potassium levels. Cultured neurons with no sign of MCMV infection showed attenuated synaptic signaling after infection of the underlying astrocyte substrate, and intercellular communication between astrocytes with no sign of infection was reduced by the presence of infected glia. These bystander effects would tend to cause further deterioration of cellular communication in the brain in addition to the problems caused by the loss of directly infected cells.

scholarly journals Manipulation of the ATP pool as a tool for metabolic engineering

2015 ◽  
Vol 43 (6) ◽  
pp. 1140-1145 ◽  
Author(s):  
Oliver Hädicke ◽  
Steffen Klamt
Keyword(s):  
Metabolic Engineering ◽  
Product Yield ◽  
Volumetric Productivity ◽  
Special Focus ◽  
Process Performance ◽  
Performance Parameters ◽  
Cofactor Engineering ◽  
Atp Pool ◽  
Fine Tune

Cofactor engineering has been long identified as a valuable tool for metabolic engineering. Besides interventions targeting the pools of redox cofactors, many studies addressed the adenosine pools of microorganisms. In this mini-review, we discuss interventions that manipulate the availability of ATP with a special focus on ATP wasting strategies. We discuss the importance to fine-tune the ATP yield along a production pathway to balance process performance parameters like product yield and volumetric productivity.

Lysophosphatidylinositol: a novel link between ABC transporters and G-protein-coupled receptors

2014 ◽  
Vol 42 (5) ◽  
pp. 1372-1377 ◽  
Author(s):  
Emily L. Ruban ◽  
Riccardo Ferro ◽  
Syamsul Ahmad Arifin ◽  
Marco Falasca
Keyword(s):  
Cell Proliferation ◽  
G Protein ◽  
Cancer Progression ◽  
Multidrug Resistance Protein 1 ◽  
Autocrine Loop ◽  
Cell Functions ◽  
Cytosolic Phospholipase ◽  
Signalling Cascades ◽  
Novel Strategy ◽  
G Protein Coupled

Lysophosphatidylinositol (LPI) is a well-known bioactive lipid that is able to activate signalling cascades relevant to cell proliferation, migration, survival and tumorigenesis. Our previous work suggested that LPI is involved in cancer progression since it can be released in the medium of Ras-transformed fibroblasts and can function as an autocrine modulator of cell growth. Different research groups have established that LPI is the specific and functional ligand for G-protein-coupled receptor 55 (GPR55) and that this GPR55–LPI axis is able to activate signalling cascades that are relevant for different cell functions. Work in our laboratory has recently unravelled an autocrine loop, by which LPI synthesized by cytosolic phospholipase A2 (cPLA2) is pumped out of the cell by ATP-binding cassette (ABC) transporter C1 (ABCC1)/multidrug resistance protein 1 (MRP1), initiating a signalling cascade downstream of GPR55. Our current work suggests that blockade of this pathway may represent a novel strategy to inhibit cancer cell proliferation.

scholarly journals Regulating quantal size of neurotransmitter release through a GPCR voltage sensor

2020 ◽  
Vol 117 (43) ◽  
pp. 26985-26995 ◽  
Author(s):  
Quanfeng Zhang ◽  
Bing Liu ◽  
Yinglin Li ◽  
Lili Yin ◽  
Muhammad Younus ◽  
...  
Keyword(s):  
G Protein ◽  
Direct Interaction ◽  
Membrane Voltage ◽  
Dense Core Vesicle ◽  
Cell Functions ◽  
Quantal Size ◽  
Per Se ◽  
Adrenal Chromaffin ◽  
Myocyte Contractility ◽  
G Protein Coupled

Current models emphasize that membrane voltage (Vm) depolarization-induced Ca2+ influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Giβγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca2+, Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y12 receptors. D76 and D127 in P2Y12 were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm → P2Y12(D76/D127) → Giβγ → QS → myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs.

scholarly journals Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

2007 ◽  
Vol 7 ◽  
pp. 1073-1081 ◽  
Author(s):  
Luigi F. Agnati ◽  
Giuseppina Leo ◽  
Susanna Genedani ◽  
Diego Guidolin ◽  
Nicola Andreoli ◽  
...  
Keyword(s):  
Immune System ◽  
G Protein ◽  
Cell Metabolism ◽  
G Protein Coupled Receptors ◽  
Host Cells ◽  
Receptor Function ◽  
Viral Receptor ◽  
Receptor Interactions ◽  
Induced Changes ◽  
G Protein Coupled

It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers), but clusters of receptors (receptor mosaics), altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

scholarly journals Brain network dynamics are hierarchically organized in time

2017 ◽  
Vol 114 (48) ◽  
pp. 12827-12832 ◽  
Author(s):  
Diego Vidaurre ◽  
Stephen M. Smith ◽  
Mark W. Woolrich
Keyword(s):  
Large Scale ◽  
Temporal Dynamics ◽  
Brain Network ◽  
Specific Measure ◽  
Brain Areas ◽  
Neuronal Populations ◽  
Subject Specific ◽  
Large Scale Networks ◽  
Network Patterns ◽  
The Brain

The brain recruits neuronal populations in a temporally coordinated manner in task and at rest. However, the extent to which large-scale networks exhibit their own organized temporal dynamics is unclear. We use an approach designed to find repeating network patterns in whole-brain resting fMRI data, where networks are defined as graphs of interacting brain areas. We find that the transitions between networks are nonrandom, with certain networks more likely to occur after others. Further, this nonrandom sequencing is itself hierarchically organized, revealing two distinct sets of networks, or metastates, that the brain has a tendency to cycle within. One metastate is associated with sensory and motor regions, and the other involves areas related to higher order cognition. Moreover, we find that the proportion of time that a subject spends in each brain network and metastate is a consistent subject-specific measure, is heritable, and shows a significant relationship with cognitive traits.

scholarly journals Nuclear GPCRs in cardiomyocytes: an insider's view of β-adrenergic receptor signaling

2011 ◽  
Vol 301 (5) ◽  
pp. H1754-H1764 ◽  
Author(s):  
George Vaniotis ◽  
Bruce G. Allen ◽  
Terence E. Hébert
Keyword(s):  
Subcellular Localization ◽  
G Protein ◽  
G Proteins ◽  
Adrenergic Receptor ◽  
Physiological State ◽  
Signaling Cascades ◽  
Special Focus ◽  
The Novel ◽  
Receptor Signaling ◽  
G Protein Coupled

In recent years, we have come to appreciate the complexity of G protein-coupled receptor signaling in general and β-adrenergic receptor (β-AR) signaling in particular. Starting originally from three β-AR subtypes expressed in cardiomyocytes with relatively simple, linear signaling cascades, it is now clear that there are large receptor-based networks which provide a rich and diverse set of responses depending on their complement of signaling partners and the physiological state. More recently, it has become clear that subcellular localization of these signaling complexes also enriches the diversity of phenotypic outcomes. Here, we review our understanding of the signaling repertoire controlled by nuclear β-AR subtypes as well our understanding of the novel roles for G proteins themselves in the nucleus, with a special focus, where possible, on their effects in cardiomyocytes. Finally, we discuss the potential pathological implications of alterations in nuclear β-AR signaling.

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